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Sample records for 2-encoded type iii

  1. Lysogeny with Shiga toxin 2-encoding bacteriophages represses type III secretion in enterohemorrhagic Escherichia coli.

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    Xuefang Xu

    Full Text Available Lytic or lysogenic infections by bacteriophages drive the evolution of enteric bacteria. Enterohemorrhagic Escherichia coli (EHEC have recently emerged as a significant zoonotic infection of humans with the main serotypes carried by ruminants. Typical EHEC strains are defined by the expression of a type III secretion (T3S system, the production of Shiga toxins (Stx and association with specific clinical symptoms. The genes for Stx are present on lambdoid bacteriophages integrated into the E. coli genome. Phage type (PT 21/28 is the most prevalent strain type linked with human EHEC infections in the United Kingdom and is more likely to be associated with cattle shedding high levels of the organism than PT32 strains. In this study we have demonstrated that the majority (90% of PT 21/28 strains contain both Stx2 and Stx2c phages, irrespective of source. This is in contrast to PT 32 strains for which only a minority of strains contain both Stx2 and 2c phages (28%. PT21/28 strains had a lower median level of T3S compared to PT32 strains and so the relationship between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This regulation was confirmed in an E. coli K12 background transduced with a marked Stx2 phage followed by measurement of a T3S reporter controlled by induced levels of the LEE-encoded regulator (Ler. The presence of an integrated Stx2 phage was shown to repress Ler induction of LEE1 and this regulation involved the CII phage regulator. This repression could be relieved by ectopic expression of a cognate CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and secreted effector proteins.

  2. Lysogeny with Shiga toxin 2-encoding bacteriophages represses type III secretion in enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Xu, Xuefang; McAteer, Sean P; Tree, Jai J; Shaw, Darren J; Wolfson, Eliza B K; Beatson, Scott A; Roe, Andrew J; Allison, Lesley J; Chase-Topping, Margo E; Mahajan, Arvind; Tozzoli, Rosangela; Woolhouse, Mark E J; Morabito, Stefano; Gally, David L

    2012-01-01

    Lytic or lysogenic infections by bacteriophages drive the evolution of enteric bacteria. Enterohemorrhagic Escherichia coli (EHEC) have recently emerged as a significant zoonotic infection of humans with the main serotypes carried by ruminants. Typical EHEC strains are defined by the expression of a type III secretion (T3S) system, the production of Shiga toxins (Stx) and association with specific clinical symptoms. The genes for Stx are present on lambdoid bacteriophages integrated into the E. coli genome. Phage type (PT) 21/28 is the most prevalent strain type linked with human EHEC infections in the United Kingdom and is more likely to be associated with cattle shedding high levels of the organism than PT32 strains. In this study we have demonstrated that the majority (90%) of PT 21/28 strains contain both Stx2 and Stx2c phages, irrespective of source. This is in contrast to PT 32 strains for which only a minority of strains contain both Stx2 and 2c phages (28%). PT21/28 strains had a lower median level of T3S compared to PT32 strains and so the relationship between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This regulation was confirmed in an E. coli K12 background transduced with a marked Stx2 phage followed by measurement of a T3S reporter controlled by induced levels of the LEE-encoded regulator (Ler). The presence of an integrated Stx2 phage was shown to repress Ler induction of LEE1 and this regulation involved the CII phage regulator. This repression could be relieved by ectopic expression of a cognate CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and secreted effector proteins.

  3. Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane.

    Science.gov (United States)

    Gallois, A; Klein, J R; Allen, L A; Jones, B D; Nauseef, W M

    2001-05-01

    Salmonella typhimurium requires a type III secretion system encoded by pathogenicity island (SPI)-2 to survive and proliferate within macrophages. This survival implies that S. typhimurium avoids or withstands bactericidal events targeted to the microbe-containing vacuole, which include intraphagosomal production of reactive oxygen species (ROS), phagosomal acidification, and delivery of hydrolytic enzymes to the phagosome via fusion with lysosomes. Recent evidence suggests that S. typhimurium alters ROS production by murine macrophages in an SPI-2-dependent manner. To gain insights into the mechanism by which S. typhimurium inhibits intraphagosomal ROS production, we analyzed the subcellular distribution of NADPH oxidase components during infection of human monocyte-derived macrophages by wild-type (WT) or several SPI-2 mutant strains of S. typhimurium. We found that the membrane component of the NADPH oxidase, flavocytochrome b(558), was actively excluded or rapidly removed from the phagosomal membrane of WT-infected monocyte-derived macrophages, thereby preventing assembly of the NADPH oxidase complex and intraphagosomal production of superoxide anion. In contrast, the NADPH oxidase assembled on and generated ROS in phagosomes containing SPI-2 mutant S. typhimurium. Subversion of NADPH oxidase assembly by S. typhimurium was accompanied by increased bacterial replication relative to that of SPI-2 mutant strains, suggesting that the ability of WT S. typhimurium to prevent NADPH oxidase assembly at the phagosomal membrane represents an important virulence factor influencing its intracellular survival.

  4. The Salmonella pathogenicity island 2-encoded type III secretion system is essential for the survival of Salmonella enterica serovar Typhimurium in free-living amoebae.

    Science.gov (United States)

    Bleasdale, Benjamin; Lott, Penelope J; Jagannathan, Aparna; Stevens, Mark P; Birtles, Richard J; Wigley, Paul

    2009-03-01

    Free-living amoebae represent a potential reservoir and predator of Salmonella enterica. Through the use of type III secretion system (T3SS) mutants and analysis of transcription of selected T3SS genes, we demonstrated that the Salmonella pathogenicity island 2 is highly induced during S. enterica serovar Typhimurium infection of Acanthamoeba polyphaga and is essential for survival within amoebae.

  5. SseA is a chaperone for the SseB and SseD translocon components of the Salmonella pathogenicity-island-2-encoded type III secretion system.

    Science.gov (United States)

    Ruiz-Albert, Javier; Mundy, Rosanna; Yu, Xiu-Jun; Beuzón, Carmen R; Holden, David W

    2003-05-01

    The type III secretion system (TTSS) encoded by the Salmonella pathogenicity island 2 (SPI-2) is required for bacterial replication inside macrophages and for systemic infection in mice. Many TTSS secreted proteins, including effectors and components of the translocon, require chaperones which promote their stability, prevent their premature interactions or facilitate their secretion. In this study, the function of the first gene (sseA) of one of the SPI-2 operons (sseA-G) was investigated. This operon includes genes that encode translocon components (SseB, SseC and SseD), translocated proteins (SseF and SseG) and putative chaperones (SscA and SscB). sseA encodes a 12.5 kDa protein with a C-terminal region with the potential to form a coiled-coil structure, but no sequence similarity to other proteins. Mutation of sseA results in severe virulence attenuation and an intracellular replication defect. It is shown here that SseA is not a secreted protein, but is required for SPI-2-dependent translocation of two effector proteins (SifA and PipB). Furthermore, the translocon components SseB and SseD were not detected in an sseA mutant strain. By using a yeast two-hybrid assay and column binding experiments, it is demonstrated that SseA interacts directly with SseB and SseD. These results indicate that SseA is a chaperone for SseB and SseD. The inability of an sseA mutant to assemble the SPI-2 TTSS translocon accounts for its high level of virulence attenuation in vivo. To the authors' knowledge, this is the first chaperone described for the SPI-2 TTSS.

  6. The type III manufactory

    CERN Document Server

    Palcoux, Sébastien

    2011-01-01

    Using unusual objects in the theory of von Neumann algebra, as the chinese game Go or the Conway game of life (generalized on finitely presented groups), we are able to build, by hands, many type III factors.

  7. Genetics Home Reference: mucopolysaccharidosis type III

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions mucopolysaccharidosis type III mucopolysaccharidosis type III Enable Javascript to view the expand/ ... boxes. Print All Open All Close All Description Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo ...

  8. Glycosaminoglycans and mucopolysaccharidosis type III.

    Science.gov (United States)

    Jakobkiewicz-Banecka, Joanna; Gabig-Ciminska, Magdalena; Kloska, Anna; Malinowska, Marcelina; Piotrowska, Ewa; Banecka-Majkutewicz, Zyta; Banecki, Bogdan; Wegrzyn, Alicja; Wegrzyn, Grzegorz

    2016-01-01

    Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is a lysosomal storage disease in which heparan sulfate is accumulated in lysosomes, as well as outside of cells, as the primary storage material. This disease is a complex of four conditions caused by dysfunctions of one of genes coding for lysosomal enzymes involved in degradation of heparan sulfate: SGSH (coding for heparan N-sulfatase) - causing MPS IIIA, NAGLU (coding for alpha-N-acetylglucosaminidase) - causing MPS IIIB, HGSNAT (coding for acetyl CoA alpha-glucosaminide acetyltransferase) - causing MPS IIIC), and GNS (coding for N-acetylglucosamine-6-sulfatase) - causing MPS IIID. The primary storage is responsible for some disease symptoms, but other arise as a result of secondary storage, including glycosphingolipids, and subsequent processes, like oxidative stress and neuroinflammation. Central nervous system is predominantly affected in all subtypes of MPS III. Heparan sulfate and its derivatives are the most commonly used biomarkers for diagnosis and prediction procedures. Currently, there is no therapy for Sanfilippo syndrome, however, clinical trials are ongoing for enzyme replacement therapy, gene therapy and substrate reduction therapy (particularly gene expression-targeted isoflavone therapy). PMID:27100513

  9. Coronal type III radio bursts and their X-ray flare and interplanetary type III counterparts

    CERN Document Server

    Reid, Hamish A S

    2016-01-01

    Type III bursts and hard X-rays are both produced by flare energetic electron beams. The link between both emissions has been investigated in many previous studies, but no statistical studies have compared both coronal and interplanetary type III bursts with X-ray flares. Using coronal radio events above 100 MHz exclusively from type III bursts, we revisited long-standing questions: Do all coronal type III bursts have X-ray counterparts. What correlation, if any, occurs between radio and X-ray intensities. What X-ray and radio signatures above 100 MHz occur in connection with interplanetary type III bursts below 14 MHz. We analysed data from 2002 to 2011 starting with coronal type III bursts above 100 MHz. We used RHESSI X-ray data greater than 6 keV to make a list of 321 events that have associated type III bursts and X-ray flares, encompassing at least 28 percent of the initial sample of type III events. We examined the timings, intensities, associated GOES class, and any interplanetary radio signature. For...

  10. NNMSM type-II and -III

    Energy Technology Data Exchange (ETDEWEB)

    Haba, Naoyuki [Graduate School of Science and Engineering, Shimane University, Matsue, Shimane (Japan); Hokkaido University, Department of Physics, Faculty of Science, Sapporo, Hokkaido (Japan); Kaneta, Kunio [Hokkaido University, Department of Physics, Faculty of Science, Sapporo, Hokkaido (Japan); University of Tokyo, Kavli Institute for the Physics and Mathematics of the Universe (WPI), Kashiwa, Chiba (Japan); Osaka University, Department of Physics, Graduate School of Science, Toyonaka, Osaka (Japan); Takahashi, Ryo [Hokkaido University, Department of Physics, Faculty of Science, Sapporo, Hokkaido (Japan)

    2014-01-15

    We suggest two types of extension of the standard model, which are the so-called next to new minimal standard model type-II and -III. They can achieve gauge coupling unification as well as suitable dark matter abundance, small neutrino masses, baryon asymmetry of the universe, inflation, and dark energy. The gauge coupling unification can be realized by introducing two or three extra new fields, and they could explain charge quantization. We also show that there are regions in which the vacuum stability, coupling perturbativity, and correct dark matter abundance can be realized with current experimental data at the same time. (orig.)

  11. Type III Societies (Apparently) Do Not Exist

    CERN Document Server

    Lacki, Brian C

    2016-01-01

    [Abridged] Whether technological societies remain small and planet-bound like our own, or ultimately span across galaxies is an open question in the Search for Extraterrestrial Intelligence. Societies that engineer on a galactic scale are classified as Type III on Kardashev's scale. I argue that Type III societies can take the form of blackboxes, entire galaxies veiled in an opaque screen. A blackbox has a temperature that is just above that of the cosmic microwave background. The screen can be made from artificial dust pervading the galaxy. I show that there is enough material in galaxies to build blackboxes if the dust is fashioned into dipole antennas. The thermal emission of a blackbox makes it a bright microwave source. I examine the Planck Catalog of Compact Sources to constrain the abundance of blackboxes. None of the 100 GHz sources has the spectrum expected of a blackbox. The null result rules out shrouded galaxy clusters out to z ~ 1 and shrouded Milky Ways out to (comoving) 700 Mpc. The reach of th...

  12. Sources of type III solar microwave bursts

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    Zhdanov, Dmitriy; Lesovoi, Sergey; Tokhchukova, Susanna

    2016-06-01

    Microwave fine structures allow us to study plasma evolution in an energy release region. The Siberian Solar Radio Telescope (SSRT) is a unique instrument designed to examine fine structures at 5.7 GHz. A complex analysis of data from RATAN-600, 4-8 GHz spectropolarimeter, and SSRT, simultaneously with extreme UV data, made it possible to localize sources of III type microwave drift bursts in August 10, 2011 event within the entire frequency band of burst occurrences, as well as to determine the most probable region of primary energy release. To localize sources of III type bursts from RATAN-600 data, an original method for data processing has been worked out. At 5.7 GHz, the source of bursts was determined along two coordinates whereas at 4.5, 4.7, 4.9, 5.1, 5.3, 5.5 and 6.0 GHz, their locations were identified along one coordinate. The size of the burst source at 5.1 GHz was found to be maximum as compared to source sizes at other frequencies.

  13. Type III apical transportation of root canal

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    Shiv P Mantri

    2012-01-01

    Full Text Available Procedural accidents leading to complications such as canal transportation have been ascribed to inapt cleaning and shaping concepts. Canal transportation is an undesirable deviation from the natural canal path. Herewith a case of apical transportation of root canal resulting in endodontic retreatment failure and its management is presented. A healthy 21-year-old young male presented discomfort and swelling associated with painful endodontically retreated maxillary incisor. Radiograph revealed periradicular radiolucency involving underfilled 11 and overfilled 12. Insufficiently obturated 11 exhibited apical transportation of canal. This type III transportation was treated by periradicular surgery and repair using white mineral trioxide aggregate (MTA. Comfortable asymptomatic patient presented uneventful healing at third and fourth month recall visits. A decrease in the size of radiolucency in radiograph supported the clinical finding. In the present case, MTA is useful in repairing the transportation defect. The result of these procedures is predictable and successful.

  14. Type III Collagen, a Fibril Network Modifier in Articular Cartilage*

    OpenAIRE

    Wu, Jiann-Jiu; Weis, Mary Ann; Kim, Lammy S.; Eyre, David R.

    2010-01-01

    The collagen framework of hyaline cartilages, including articular cartilage, consists largely of type II collagen that matures from a cross-linked heteropolymeric fibril template of types II, IX, and XI collagens. In the articular cartilages of adult joints, type III collagen makes an appearance in varying amounts superimposed on the original collagen fibril network. In a study to understand better the structural role of type III collagen in cartilage, we find that type III collagen molecules...

  15. Autism Symptoms Related to Tyrosinemia Type III: A Case Report

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    Ayşegül Yolga Tahiroğlu

    2008-08-01

    Full Text Available The published literature on tyrosinemia type III consists of only a few case reports. In this report, we present a patient with tyrosinemia type III, autism, and mental retardation. This patient’s speech improved and his autistic symptoms lessened on a tyrosine-restricted diet, although his mental retardation remained unchanged. This is the first published report of a patient with tyrosinemia type III and autism. This observation is significant due to the paucity of published information about tyrosinemia type III. Turk Jem 2008; 12: 55-6

  16. Diverse intracellular pathogens activate type III interferon expression from peroxisomes.

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    Odendall, Charlotte; Dixit, Evelyn; Stavru, Fabrizia; Bierne, Helene; Franz, Kate M; Durbin, Ann Fiegen; Boulant, Steeve; Gehrke, Lee; Cossart, Pascale; Kagan, Jonathan C

    2014-08-01

    Type I interferon responses are considered the primary means by which viral infections are controlled in mammals. Despite this view, several pathogens activate antiviral responses in the absence of type I interferons. The mechanisms controlling type I interferon-independent responses are undefined. We found that RIG-I like receptors (RLRs) induce type III interferon expression in a variety of human cell types, and identified factors that differentially regulate expression of type I and type III interferons. We identified peroxisomes as a primary site of initiation of type III interferon expression, and revealed that the process of intestinal epithelial cell differentiation upregulates peroxisome biogenesis and promotes robust type III interferon responses in human cells. These findings highlight the importance of different intracellular organelles in specific innate immune responses.

  17. The expression of type III hyperlipoproteinemia: Involvement of lipolysis genes

    NARCIS (Netherlands)

    Henneman, P.; Sman-de Beer, F. van der; Moghaddam, P.H.; Huijts, P.; Stalenhoef, A.F.H.; Kastelein, J.J.P.; Duijn, C.M. van; Havekes, L.M.; Frants, R.R.; Dijk, K.W. van; Smelt, A.H.M.

    2009-01-01

    Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic li

  18. Assessment of Sleep in Children with Mucopolysaccharidosis Type III

    OpenAIRE

    Mahon, Louise Victoria; Lomax, Michelle; Grant, Sheena; Cross, Elaine; Hare, Dougal Julian; Wraith, James Ed; Jones, Simon; Bigger, Brian; Langford-Smith, Kia; Canal, Maria

    2014-01-01

    Sleep disturbances are prevalent in mucopolysaccharidosis Type III (MPS III), yet there is a lack of objective, ecologically valid evidence detailing sleep quantity, quality or circadian system. Eight children with MPS III and eight age-matched typically developing children wore an actigraph for 7–10 days/nights. Saliva samples were collected at three time-points on two separate days, to permit analysis of endogenous melatonin levels. Parents completed a sleep questionnaire and a daily sleep ...

  19. Cognitive development in patients with Mucopolysaccharidosis type III (Sanfilippo syndrome)

    OpenAIRE

    Colland Vivian; Grootenhuis Martha; Marchal Jan; Valstar Marlies J; Wijburg Frits A

    2011-01-01

    Abstract Background Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder caused by a deficiency of one of the enzymes involved in the degradation of heparan sulfate. MPS III is characterized by progressive mental deterioration resulting in severe dementia. A number of potentially disease-modifying therapies are studied. As preservation of cognitive function is the ultimate goal of treatment, assessment of cognitive development will be essential in orde...

  20. Extrapyramidal Symptoms and Medication Use in Mucopolysaccharidosis Type III

    Science.gov (United States)

    Tchan, Michel C.; Sillence, David

    2009-01-01

    Background: We report the case of a 16-year-old male with Mucopolysaccharidosis III type A (Sanfilippo syndrome) who was commenced on risperidone for behaviour management. He rapidly developed extrapyramidal symptoms that have not resolved. Method: The medication histories of 20 patients with Mucopolysaccharidosis III seen at a Lysosomal Storage…

  1. Relevance of the type III error in epidemiological maps

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    Heinzl Harald

    2012-08-01

    Full Text Available Abstract Background A type III error arises from a two-sided test, when one side is erroneously favoured although the true effect actually resides on the other side. The relevance of this grave error in decision-making is studied for epidemiological maps. Results Theoretical considerations confirm that a type III error may be large for regions with small numbers of expected cases even when no spatial smoothing has been performed. A simulation study based on infant mortality data in Austria reveals that spatial smoothing may additionally increase the risk of type III errors. Conclusions The occurrence of a type III error should be taken into account when interpreting results presented in epidemiological maps, particularly with regard to sparsely populated regions and spatial smoothing.

  2. Guarding the frontiers: the biology of type III interferons

    DEFF Research Database (Denmark)

    Wack, Andreas; Terczynska-Dyla, Ewa; Hartmann, Rune

    2015-01-01

    Type III interferons (IFNs) or IFN-λs regulate a similar set of genes as type I IFNs, but whereas type I IFNs act globally, IFN-λs primarily target mucosal epithelial cells and protect them against the frequent viral attacks that are typical for barrier tissues. IFN-λs thereby help to maintain...

  3. Type III factors with unique Cartan decomposition

    CERN Document Server

    Houdayer, Cyril

    2012-01-01

    We prove that for any free ergodic nonsingular nonamenable action \\Gamma\\ \\actson (X,\\mu) of all \\Gamma\\ in a large class of groups including all hyperbolic groups, the associated group measure space factor $L^\\infty(X) \\rtimes \\Gamma$ has L^\\infty(X) as its unique Cartan subalgebra, up to unitary conjugacy. This generalizes the probability measure preserving case that was established in [PV12]. We also prove primeness and indecomposability results for such crossed products, for the corresponding orbit equivalence relations and for arbitrary amalgamated free products $M_1 *_B M_2$ over a subalgebra B of type I.

  4. Sanfilippo disease (mucopolysaccharidosis type III): Early diagnosis and treatment

    OpenAIRE

    Wijburg, F.A.; Ruijter, de, J.

    2013-01-01

    Mucopolysaccharidoses (MPS) are severe, inherited metabolic disorders caused by defective lysosomal degradation glycosaminoglycans (GAGs). The subsequent progressive accumulation of GAGs in cells and tissues in MPS patients results in extensive, severe and progressive disease, generally limiting quality of life and life expectancy. Sanfilippo disease (mucopolysaccharidosis type III, MPS III) is one of the 7 MPSs and is characterized by storage of the GAG heparan sulfate (HS), primarily leadin...

  5. Multiple Gastric Carcinomas Associated with Potter Type III Cystic Disease

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    Kenji Mimatsu

    2011-10-01

    Full Text Available We report a case of multiple gastric carcinomas associated with Potter type III cystic disease of the liver, mesenterium and kidney. A 65-year-old man with chronic renal failure due to polycystic kidneys and under hemodialysis treatment 3 times a week for 2 years was admitted to our hospital because of anemia. He stated that his sister had suffered from polycystic kidney disease. Gastrointestinal fiberscopy showed two lesions in the lesser curvature in the lower portion of the stomach, and histopathological analysis of the gastric tumor biopsies revealed that one of the tumors was a papillary adenocarcinoma and the other a poorly differentiated adenocarcinoma. Helicobacter pylori infection was not detected in the stomach mucosa. Abdominal computed tomography scan revealed polycystic lesions in the liver, mesenterium and both kidneys. These imaging findings and family history suggested that the patient suffered from multiple gastric carcinomas associated with Potter type III cystic disease of the liver, mesenterium and kidney. Reports on the association of malignant neoplasm with Potter type III cystic disease are extremely rare. Especially, no case of the association of gastric carcinoma with Potter type III cystic disease of the liver and kidney has been described previously. This is a first report of the association of gastric carcinoma with Potter type III cystic disease. We also review reports of other malignant neoplasms associated with polycystic disease.

  6. Assessment of Sleep in Children with Mucopolysaccharidosis Type III

    Science.gov (United States)

    Mahon, Louise Victoria; Lomax, Michelle; Grant, Sheena; Cross, Elaine; Hare, Dougal Julian; Wraith, James Ed; Jones, Simon; Bigger, Brian; Langford-Smith, Kia; Canal, Maria

    2014-01-01

    Sleep disturbances are prevalent in mucopolysaccharidosis Type III (MPS III), yet there is a lack of objective, ecologically valid evidence detailing sleep quantity, quality or circadian system. Eight children with MPS III and eight age-matched typically developing children wore an actigraph for 7–10 days/nights. Saliva samples were collected at three time-points on two separate days, to permit analysis of endogenous melatonin levels. Parents completed a sleep questionnaire and a daily sleep diary. Actigraphic data revealed that children with MPS III had significantly longer sleep onset latencies and greater daytime sleep compared to controls, but night-time sleep duration did not differ between groups. In the MPS III group, sleep efficiency declined, and sleep onset latency increased, with age. Questionnaire responses showed that MPS III patients had significantly more sleep difficulties in all domains compared to controls. Melatonin concentrations showed an alteration in the circadian system in MPS III, which suggests that treatment for sleep problems should attempt to synchronise the sleep-wake cycle to a more regular pattern. Actigraphy was tolerated by children and this monitoring device can be recommended as a measure of treatment success in research and clinical practice. PMID:24504123

  7. Assessment of sleep in children with mucopolysaccharidosis type III.

    Directory of Open Access Journals (Sweden)

    Louise Victoria Mahon

    Full Text Available Sleep disturbances are prevalent in mucopolysaccharidosis Type III (MPS III, yet there is a lack of objective, ecologically valid evidence detailing sleep quantity, quality or circadian system. Eight children with MPS III and eight age-matched typically developing children wore an actigraph for 7-10 days/nights. Saliva samples were collected at three time-points on two separate days, to permit analysis of endogenous melatonin levels. Parents completed a sleep questionnaire and a daily sleep diary. Actigraphic data revealed that children with MPS III had significantly longer sleep onset latencies and greater daytime sleep compared to controls, but night-time sleep duration did not differ between groups. In the MPS III group, sleep efficiency declined, and sleep onset latency increased, with age. Questionnaire responses showed that MPS III patients had significantly more sleep difficulties in all domains compared to controls. Melatonin concentrations showed an alteration in the circadian system in MPS III, which suggests that treatment for sleep problems should attempt to synchronise the sleep-wake cycle to a more regular pattern. Actigraphy was tolerated by children and this monitoring device can be recommended as a measure of treatment success in research and clinical practice.

  8. Tyrosinemia Type III detected via neonatal screening: management and outcome.

    Science.gov (United States)

    Heylen, Evelyne; Scherer, Gerd; Vincent, Marie-Françoise; Marie, Sandrine; Fischer, Judith; Nassogne, Marie-Cécile

    2012-11-01

    Tyrosinemia Type III is caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), an enzyme involved in the catabolic pathway of tyrosine. To our knowledge, only a few patients presenting with this disease have been described in the literature, and the clinical phenotype remains variable and unclear. We report the case of a boy with tyrosinemia Type III detected using neonatal screening, who is homozygous for the splice donor mutation IVS11+1G>A in intron 11 of the HPD gene. At the age of 30 months, the boy's outcome under mild protein restriction was characterized by normal growth and psychomotor development.

  9. Type III von Neumann Algebras associated with $\\O_\\theta$

    CERN Document Server

    Yang, Dilian

    2011-01-01

    Let $\\Fth$ be a 2 graph generated by $m$ blue edges and $n$ red edges, and $\\omega$ be the distinguished faithful state associated with its graph C*-algebra $\\O_\\theta$. In this paper, we characterize the factorness of the von Neumann algebra $\\pi_\\omega(\\O_\\theta)"$ induced from the GNS representation of $\\omega$ under a certain condition. Moreover, when $\\pi_\\omega(\\O_\\theta)"$ is a factor, then it is of type III$_{m^{-\\frac{1}{b}}}$ (or III$_{n^{-\\frac{1}{a}}}$) if $\\frac{\\ln m}{\\ln n}\\in\\bQ$, where $a,b\\in\\bN$ with $\\gcd(a,b)=1$ satisfy $m^a=n^b$, and of type III$_1$ if $\\frac{\\ln m}{\\ln n}\

  10. Interplanetary density models as inferred from solar Type III bursts

    Science.gov (United States)

    Oppeneiger, Lucas; Boudjada, Mohammed Y.; Lammer, Helmut; Lichtenegger, Herbert

    2016-04-01

    We report on the density models derived from spectral features of solar Type III bursts. They are generated by beams of electrons travelling outward from the Sun along open magnetic field lines. Electrons generate Langmuir waves at the plasma frequency along their ray paths through the corona and the interplanetary medium. A large frequency band is covered by the Type III bursts from several MHz down to few kHz. In this analysis, we consider the previous empirical density models proposed to describe the electron density in the interplanetary medium. We show that those models are mainly based on the analysis of Type III bursts generated in the interplanetary medium and observed by satellites (e.g. RAE, HELIOS, VOYAGER, ULYSSES,WIND). Those models are confronted to stereoscopic observations of Type III bursts recorded by WIND, ULYSSES and CASSINI spacecraft. We discuss the spatial evolution of the electron beam along the interplanetary medium where the trajectory is an Archimedean spiral. We show that the electron beams and the source locations are depending on the choose of the empirical density models.

  11. Microwave Type III Pair Bursts in Solar Flares

    CERN Document Server

    Tan, Baolin; Karlicky, Marian; Huang, Guangli; Tan, Chengming

    2016-01-01

    Solar microwave type III pair burst is composed of normal and reverse-sloped (RS) burst branches with oppositely fast frequency drifts. It is the most sensitive signature of the primary energy release and electron accelerations in flares. This work reported 11 microwave type III pair events in 9 flares observed by radio spectrometers in China and the Czech Republic at frequency of 0.80 - 7.60 GHz during 1994 - 2014. These type III pairs occurred in flare impulsive and postflare phases with separate frequency in range of 1.08 - 3.42 GHz and frequency gap 10 - 1700 MHz. The frequency drift increases with the separate frequency (f_{x}), the lifetime of each burst is anti-correlated to f_{x}, while the frequency gap is independent to f_{x}. In most events, the normal branches are drifting obviously faster than the RS branches. The type III pairs occurring in flare impulsive phase have lower separate frequency, longer lifetime, wider frequency gap, and slower frequency drift than that occurring in postflare phase....

  12. A tiny event producing an interplanetary type III burst

    CERN Document Server

    Alissandrakis, C E; Patsourakos, S; Kontogeorgos, A; Tsitsipis, P

    2015-01-01

    We investigate the conditions under which small scale energy release events in the low corona gave rise to strong interplanetary (IP) type III bursts. We analyze observations of three tiny events, detected by the Nan\\c cay Radio Heliograph (NRH), two of which produced IP type IIIs. We took advantage of the NRH positioning information and of the high cadence of AIA/SDO data to identify the associated EUV emissions. We measured positions and time profiles of the metric and EUV sources. We found that the EUV events that produced IP type IIIs were located near a coronal hole boundary, while the one that did not was located in a closed magnetic field region. In all three cases tiny flaring loops were involved, without any associated mass eruption. In the best observed case the radio emission at the highest frequency (435 MHz) was displaced by ~55" with respect to the small flaring loop. The metric type III emission shows a complex structure in space and in time, indicative of multiple electron beams, despite the l...

  13. Microwave Type III Pair Bursts in Solar Flares

    Science.gov (United States)

    Tan, Baolin; Mészárosová, Hana; Karlický, Marian; Huang, Guangli; Tan, Chengming

    2016-03-01

    A solar microwave type III pair burst is composed of normal and reverse-sloped (RS) burst branches with oppositely fast frequency drifts. It is the most sensitive signature of the primary energy release and electron accelerations in flares. This work reports 11 microwave type III pair events in 9 flares observed by radio spectrometers in China and the Czech Republic at a frequency of 0.80-7.60 GHz during 1994-2014. These type III pairs occurred in flare impulsive and postflare phases with separate frequencies in the range of 1.08-3.42 GHz and a frequency gap of 10-1700 MHz. The frequency drift increases with the separate frequency (fx), the lifetime of each burst is anti-correlated to fx, while the frequency gap is independent of fx. In most events, the normal branches are drifting obviously faster than the RS branches. The type III pairs occurring in flare impulsive phase have lower separate frequencies, longer lifetimes, wider frequency gaps, and slower frequency drifts than that occurring in postflare phase. Also, the latter always has strong circular polarization. Further analysis indicates that near the flare energy release sites the plasma density is about {10}10{--}{10}11 cm-3 and the temperature is higher than 107 K. These results provide new constraints to the acceleration mechanism in solar flares.

  14. Cognitive development in patients with Mucopolysaccharidosis type III (Sanfilippo syndrome

    Directory of Open Access Journals (Sweden)

    Colland Vivian

    2011-06-01

    Full Text Available Abstract Background Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome is a lysosomal storage disorder caused by a deficiency of one of the enzymes involved in the degradation of heparan sulfate. MPS III is characterized by progressive mental deterioration resulting in severe dementia. A number of potentially disease-modifying therapies are studied. As preservation of cognitive function is the ultimate goal of treatment, assessment of cognitive development will be essential in order to evaluate treatment efficacy. However, no large scale studies on cognitive levels in MPS III patients, using formal psychometric tests, have been reported. Methods We aimed to assess cognitive development in all 73 living patients with MPS III in the Netherlands. Results Cognitive development could be assessed in 69 patients. In 39 of them developmental level was estimated > 3 months and formal psychometric testing was attempted. A remarkable variation in the intellectual disability was detected. Conclusions Despite special challenges encountered, testing failed in only three patients. The observed broad variation in intellectual disability, should be taken into account when designing therapeutic trials.

  15. Type II and Type III Radio Bursts and their Correlation with Solar Energetic Proton Events

    Science.gov (United States)

    Winter, L. M.; Ledbetter, K.

    2015-08-01

    Using the Wind/WAVES radio observations from 2010 to 2013, we present an analysis of the 123 decametric–hectometric (DH) type II solar radio bursts during this period, the associated type III burst properties, and their correlation with solar energetic proton (SEP) properties determined from analysis of the Geostationary Operational Environmental Satellite (GOES) observations. We present a useful catalog of the type II burst, type III burst, Langmuir wave, and proton flux properties for these 123 events, which we employ to develop a statistical relationship between the radio properties and peak proton flux that can be used to forecast SEP events. We find that all SEP events with a peak \\gt 10 MeV flux above 15 protons cm‑2 s‑1 sr‑1 are associated with a type II burst and virtually all SEP events, 92%, are also associated with a type III radio burst. Based on a principal component analysis, the radio burst properties that are most highly correlated with the occurrence of gradual SEP events and account for the most variance in the radio properties are the type III burst intensity and duration. Further, a logistic regression analysis with the radio-derived principal component (dominated by the type III and type II radio burst intensity and type III duration) obtains SEP predictions approaching the human forecaster rates, with a false alarm rate of 22%, a probability of detection of 62%, and with 85% of the classifications correct. Therefore, type III radio bursts that occur along with a DH type II burst are shown to be an important diagnostic that can be used to forecast SEP events.

  16. Evaluation of Salmonella enterica type III secretion system effector proteins as carriers for heterologous vaccine antigens.

    Science.gov (United States)

    Hegazy, Wael Abdel Halim; Xu, Xin; Metelitsa, Leonid; Hensel, Michael

    2012-03-01

    Live attenuated strains of Salmonella enterica have a high potential as carriers of recombinant vaccines. The type III secretion system (T3SS)-dependent translocation of S. enterica can be deployed for delivery of heterologous antigens to antigen-presenting cells. Here we investigated the efficacy of various effector proteins of the Salmonella pathogenicity island (SPI2)-encoded T3SS for the translocation of model antigens and elicitation of immune responses. The SPI2 T3SS effector proteins SifA, SteC, SseL, SseJ, and SseF share an endosomal membrane-associated subcellular localization after translocation. We observed that all effector proteins could be used to translocate fusion proteins with the model antigens ovalbumin and listeriolysin into the cytosol of host cells. Under in vitro conditions, fusion proteins with SseJ and SteC stimulated T-cell responses that were superior to those triggered by fusion proteins with SseF. However, in mice vaccinated with Salmonella carrier strains, only fusion proteins based on SseJ or SifA elicited potent T-cell responses. These data demonstrate that the selection of an optimal SPI2 effector protein for T3SS-mediated translocation is a critical parameter for the rational design of effective Salmonella-based recombinant vaccines.

  17. Identification of Novel Type III Effectors Using Latent Dirichlet Allocation

    Directory of Open Access Journals (Sweden)

    Yang Yang

    2012-01-01

    Full Text Available Among the six secretion systems identified in Gram-negative bacteria, the type III secretion system (T3SS plays important roles in the disease development of pathogens. T3SS has attracted a great deal of research interests. However, the secretion mechanism has not been fully understood yet. Especially, the identification of effectors (secreted proteins is an important and challenging task. This paper adopts machine learning methods to identify type III secreted effectors (T3SEs. We extract features from amino acid sequences and conduct feature reduction based on latent semantic information by using latent Dirichlet allocation model. The experimental results on Pseudomonas syringae data set demonstrate the good performance of the new methods.

  18. A plant type III polyketide synthase that produces pentaketide chromone.

    Science.gov (United States)

    Abe, Ikuro; Utsumi, Yoriko; Oguro, Satoshi; Morita, Hiroyuki; Sano, Yukie; Noguchi, Hiroshi

    2005-02-01

    A novel plant-specific type III polyketide synthase (PKS) that catalyzes formation of a pentaketide chromone, 5,7-dihydroxy-2-methylchromone, from five molecules of malonyl-CoA, was cloned and sequenced from aloe (Aloe arborescens). Site-directed mutagenesis revealed that Met207 (corresponding to Thr197 in CHS) determines the polyketide chain length and the product specificity of the enzyme; remarkably, replacement of a single amino acid residue, Met207, with Gly yielded a mutant enzyme that efficiently produces aromatic octaketides, SEK4 and SEK4b, the products of the minimal PKS for actinorhodin (act from Streptomyces coelicolor), from eight molecules of malonyl-CoA. This provided new insights into the catalytic functions and specificities of the CHS-superfamily type III PKS enzymes. PMID:15686354

  19. Multiple Gastric Carcinomas Associated with Potter Type III Cystic Disease

    OpenAIRE

    Mimatsu, Kenji; Oida, Takatsugu; Kawasaki, Atsushi; Kano, Hisao; Kida, Kazutoshi; Fukino, Nobutada; Kuboi, Youichi; Amano, Sadao

    2011-01-01

    We report a case of multiple gastric carcinomas associated with Potter type III cystic disease of the liver, mesenterium and kidney. A 65-year-old man with chronic renal failure due to polycystic kidneys and under hemodialysis treatment 3 times a week for 2 years was admitted to our hospital because of anemia. He stated that his sister had suffered from polycystic kidney disease. Gastrointestinal fiberscopy showed two lesions in the lesser curvature in the lower portion of the stomach, and hi...

  20. Assembly and function of type III secretory systems.

    Science.gov (United States)

    Cornelis, G R; Van Gijsegem, F

    2000-01-01

    Type III secretion systems allow Yersinia spp., Salmonella spp., Shigella spp., Bordetella spp., and Pseudomonas aeruginosa and enteropathogenic Escherichia coli adhering at the surface of a eukaryotic cell to inject bacterial proteins across the two bacterial membranes and the eukaryotic cell membrane to destroy or subvert the target cell. These systems consist of a secretion apparatus, made of approximately 25 proteins, and an array of proteins released by this apparatus. Some of these released proteins are "effectors," which are delivered into the cytosol of the target cell, whereas the others are "translocators," which help the effectors to cross the membrane of the eukaryotic cell. Most of the effectors act on the cytoskeleton or on intracellular-signaling cascades. A protein injected by the enteropathogenic E. coli serves as a membrane receptor for the docking of the bacterium itself at the surface of the cell. Type III secretion systems also occur in plant pathogens where they are involved both in causing disease in susceptible hosts and in eliciting the so-called hypersensitive response in resistant or nonhost plants. They consist of 15-20 Hrp proteins building a secretion apparatus and two groups of effectors: harpins and avirulence proteins. Harpins are presumably secreted in the extracellular compartment, whereas avirulence proteins are thought to be targeted into plant cells. Although a coherent picture is clearly emerging, basic questions remain to be answered. In particular, little is known about how the type III apparatus fits together to deliver proteins in animal cells. It is even more mysterious for plant cells where a thick wall has to be crossed. In spite of these haunting questions, type III secretion appears as a fascinating trans-kingdom communication device. PMID:11018143

  1. X-ray Flares and their Type III Radio Signature

    Science.gov (United States)

    Vilmer, N.; Reid, H.

    2012-12-01

    Oppositely directed accelerated electron beams in solar flares can produce Hard X-rays in the chromosphere and radio emission from the low corona to the interplanetary medium. The temporal and inferred spectral correlation of these electron beams indicates a common acceleration region. We used the RHESSI X-ray flare catalogue and the PHOENIX catalogue of radio bursts to select a list of events with impulsive X-ray signatures that was correlated in time with type III radio emission in the decimetric range. We furthermore selected events for which the Nançay Radioheliograph had spatially resolved information in the 450-150 MHz range. We investigate the percentage of decimetric/metric type III radio bursts that have a counterpart at lower frequencies (14 - 1 MHz) observed with Wind/Waves. We will discuss the electron beam characteristics deduced from X-ray observations that affect the relationship between coronal and interplanetary type III bursts. Moreover, we will use the combined images in radio and X-ray frequencies to deduce the role of the local coronal environment.

  2. Assembly of the bacterial type III secretion machinery.

    Science.gov (United States)

    Diepold, Andreas; Wagner, Samuel

    2014-07-01

    Many bacteria that live in contact with eukaryotic hosts, whether as symbionts or as pathogens, have evolved mechanisms that manipulate host cell behaviour to their benefit. One such mechanism, the type III secretion system, is employed by Gram-negative bacterial species to inject effector proteins into host cells. This function is reflected by the overall shape of the machinery, which resembles a molecular syringe. Despite the simplicity of the concept, the type III secretion system is one of the most complex known bacterial nanomachines, incorporating one to more than hundred copies of up to twenty different proteins into a multi-MDa transmembrane complex. The structural core of the system is the so-called needle complex that spans the bacterial cell envelope as a tripartite ring system and culminates in a needle protruding from the bacterial cell surface. Substrate targeting and translocation are accomplished by an export machinery consisting of various inner membrane embedded and cytoplasmic components. The formation of such a multimembrane-spanning machinery is an intricate task that requires precise orchestration. This review gives an overview of recent findings on the assembly of type III secretion machines, discusses quality control and recycling of the system and proposes an integrated assembly model.

  3. Nonlinear Spinor Fields in Bianchi type-III spacetime

    CERN Document Server

    Saha, Bijan

    2016-01-01

    Within the scope of Bianchi type-III spacetime we study the role of spinor field on the evolution of the Universe as well as the influence of gravity on the spinor field. In doing so we have considered a polynomial type of nonlinearity. In this case the spacetime remains locally rotationally symmetric and anisotropic all the time. It is found that depending on the sign of nonlinearity the models allows both accelerated and oscillatory modes of expansion. The non-diagonal components of energy-momentum tensor though impose some restrictions on metric functions and components of spinor field, unlike Bianchi type I, V and $VI_0$ cases, they do not lead to vanishing mass and nonlinear terms of the spinor field.

  4. Guadalajara camptodactyly type III: a new probably autosomal dominant syndrome.

    Science.gov (United States)

    Figuera, L E; Ramírez-Dueñas, M L; Dávalos, I P; Cantú, J M

    2002-10-01

    A Mexican family is presented with the main clinical features of camptodactyly, a distinctive facial appearance because of ocular hypertelorism, telecanthus, symblepharon and spinal defects. Other clinical manifestations included: multiple nevi, simplified ears, retrognathia, congenital shortness of the sternocleidomastoid muscle, thin hands and feet, a small penis and mild mental retardation. Radiographic studies revealed spina bifida occulta at cervical and dorso-lumbar levels, increased bone trabeculae, cortical thickening and delayed bone age. The presence of five affected members through four generations suggests autosomal dominant inheritance although no male-to-male transmission was documented. The authors propose this as a new entity, and have designated it Guadalajara camptodactyly type III.

  5. A Probable Short Decimetric Type I-like Noise Storm: Associated with Type III Bursts?

    Institute of Scientific and Technical Information of China (English)

    Rui-Xiang Xie; Min Wang; Yi-Hua Yan

    2005-01-01

    A rare Type I-like noise storm was observed with the solar radio spectrometers (1.0-2.0 GHz and 2.60-3.8 GHz) at National Astronomical Observatories of China (NAOC) on September 23, 1998. We concentrate on checking the Type I-like noise storm occurred in the decay phase of a Type IV radio burst. This noise storm consists of many Type I bursts and isolated Type III or Type III pair bursts.It has a bandwidth of ≤ 0.5 GHz. The duration of each Type I burst is of the order of 100-300ms. The total duration is greater than 11 minutes. The circular polarization degree of the components of Type I and associated Type III bursts are about 40%-100% and almost 100%, respectively, which is greater than that of the background continuum (nearly the precision of our instrument). This short decimetric Type I-like storm may be another kind or the extension of the kind of metric Type I storm, and may possess the duality of metric and decimetric radio emission. It may be in favor of an earlier emission mechanism of the fundamental plasma radiation due to the coalescence of Langmuir waves with low-frequency waves.

  6. Numerical simulations of type III planetary migration: III. Outward migration of massive planets

    CERN Document Server

    Peplinski, A; Mellema, G

    2008-01-01

    We present a numerical study of rapid, so called type III migration for Jupiter-sized planets embedded in a protoplanetary disc. We limit ourselves to the case of outward migration, and study in detail its evolution and physics, concentrating on the structure of the co-rotation and circumplanetary regions, and processes for stopping migration. We also consider the dependence of the migration behaviour on several key parameters. We perform this study using global, two-dimensional hydrodynamical simulations with adaptive mesh refinement. We find that the outward directed type III migration can be started if the initial conditions support $Z > 1$, that corresponds to initial value $M_\\rmn{\\Delta} \\ga 1.5$. Unlike the inward directed migration, in the outward migration the migration rate increases due to the growing of the volume of the co-orbital region. We find the migration to be strongly dependent on the rate of the mass accumulation in the circumplanetary disc, leading to two possible regimes of migration, f...

  7. Wave-wave interactions in solar type III radio bursts

    International Nuclear Information System (INIS)

    The high time resolution observations from the STEREO/WAVES experiment show that in type III radio bursts, the Langmuir waves often occur as localized magnetic field aligned coherent wave packets with durations of a few ms and with peak intensities well exceeding the strong turbulence thresholds. Some of these wave packets show spectral signatures of beam-resonant Langmuir waves, down- and up-shifted sidebands, and ion sound waves, with frequencies, wave numbers, and tricoherences satisfying the resonance conditions of the oscillating two stream instability (four wave interaction). The spectra of a few of these wave packets also contain peaks at fpe, 2fpe and 3 fpe (fpe is the electron plasma frequency), with frequencies, wave numbers and bicoherences (computed using the wavelet based bispectral analysis techniques) satisfying the resonance conditions of three wave interactions: (1) excitation of second harmonic electromagnetic waves as a result of coalescence of two oppositely propagating Langmuir waves, and (2) excitation of third harmonic electromagnetic waves as a result of coalescence of Langmuir waves with second harmonic electromagnetic waves. The implication of these findings is that the strong turbulence processes play major roles in beam stabilization as well as conversion of Langmuir waves into escaping radiation in type III radio bursts

  8. A Novel Type III Endosome Transmembrane Protein, TEMP

    Directory of Open Access Journals (Sweden)

    Rohan D. Teasdale

    2012-11-01

    Full Text Available As part of a high-throughput subcellular localisation project, the protein encoded by the RIKEN mouse cDNA 2610528J11 was expressed and identified to be associated with both endosomes and the plasma membrane. Based on this, we have assigned the name TEMP for Type III Endosome Membrane Protein. TEMP encodes a short protein of 111 amino acids with a single, alpha-helical transmembrane domain. Experimental analysis of its membrane topology demonstrated it is a Type III membrane protein with the amino-terminus in the lumenal, or extracellular region, and the carboxy-terminus in the cytoplasm. In addition to the plasma membrane TEMP was localized to Rab5 positive early endosomes, Rab5/Rab11 positive recycling endosomes but not Rab7 positive late endosomes. Video microscopy in living cells confirmed TEMP's plasma membrane localization and identified the intracellular endosome compartments to be tubulovesicular. Overexpression of TEMP resulted in the early/recycling endosomes clustering at the cell periphery that was dependent on the presence of intact microtubules. The cellular function of TEMP cannot be inferred based on bioinformatics comparison, but its cellular distribution between early/recycling endosomes and the plasma membrane suggests a role in membrane transport.

  9. Hereditary sensory and autonomic neuropathies: types II, III, and IV.

    Science.gov (United States)

    Axelrod, Felicia B; Gold-von Simson, Gabrielle

    2007-10-03

    The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.

  10. Hereditary sensory and autonomic neuropathies: types II, III, and IV

    Directory of Open Access Journals (Sweden)

    Axelrod Felicia B

    2007-10-01

    Full Text Available Abstract The hereditary sensory and autonomic neuropathies (HSAN encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating. Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III, which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive.

  11. Functional Promiscuity of Two Divergent Paralogs of Type III Plant Polyketide Synthases.

    Science.gov (United States)

    Pandith, Shahzad A; Dhar, Niha; Rana, Satiander; Bhat, Wajid Waheed; Kushwaha, Manoj; Gupta, Ajai P; Shah, Manzoor A; Vishwakarma, Ram; Lattoo, Surrinder K

    2016-08-01

    Plants effectively defend themselves against biotic and abiotic stresses by synthesizing diverse secondary metabolites, including health-protective flavonoids. These display incredible chemical diversity and ubiquitous occurrence and confer impeccable biological and agricultural applications. Chalcone synthase (CHS), a type III plant polyketide synthase, is critical for flavonoid biosynthesis. It catalyzes acyl-coenzyme A thioesters to synthesize naringenin chalcone through a polyketidic intermediate. The functional divergence among the evolutionarily generated members of a gene family is pivotal in driving the chemical diversity. Against this backdrop, this study was aimed to functionally characterize members of the CHS gene family from Rheum emodi, an endangered and endemic high-altitude medicinal herb of northwestern Himalayas. Two full-length cDNAs (1,179 bp each), ReCHS1 and ReCHS2, encoding unique paralogs were isolated and characterized. Heterologous expression and purification in Escherichia coli, bottom-up proteomic characterization, high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis, and enzyme kinetic studies using five different substrates confirmed their catalytic potential. Phylogenetic analysis revealed the existence of higher synonymous mutations in the intronless divergents of ReCHS. ReCHS2 displayed significant enzymatic efficiency (Vmax/Km) with different substrates. There were significant spatial and altitudinal variations in messenger RNA transcript levels of ReCHSs correlating positively with metabolite accumulation. Furthermore, the elicitations in the form of methyl jasmonate, salicylic acid, ultraviolet B light, and wounding, chosen on the basis of identified cis-regulatory promoter elements, presented considerable differences in the transcript profiles of ReCHSs. Taken together, our results demonstrate differential propensities of CHS paralogs in terms of the accumulation of flavonoids and

  12. Elective visceral hybrid repair of type III thoracoabdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Marjanović Ivan

    2012-01-01

    Full Text Available Introduction. According to the classification given by Crawford et al. type III thoracoabdominal aortic aneurysm (TAAA is dilatation of the aorta from the level of the rib 6 to the separation of the aorta below the renal arteries, capturing all the visceral branch of aorta. Visceral hybrid reconstruction of TAAA is a procedure developed in recent years in the world, which involves a combination of conventional, open and endovascular aortic reconstruction surgery at the level of separation of the left subclavian artery to the level of visceral branches of aorta. Case report. We presented a 75-years-old man, with elective visceral hybrid reconstruction of type III TAAA. Computerized scanning (CT angiography of the patient showed type III TAAA with the maximum transverse diameter of aneurysm of 92 mm. Aneurysm started at the level of the sixth rib, and the end of the aneurysm was 1 cm distal to the level of renal arteries. Aneurysm compressed the esophagus, causing the patient difficulty in swallowing act, especially solid food, and frequent back pain. From the other comorbidity, the patient had been treated for a long time, due to chronic obstructive pulmonary disease and hypertension. In general endotracheal anesthesia with epidural analgesia, the patient underwent visceral hybrid reconstruction of TAAA, which combines classic, open vascular surgery and endovascular procedures. Classic vascular surgery is visceral reconstruction using by-pass procedure from the distal, normal aorta to all visceral branches: celiac trunk, superior mesenteric artery and both renal arteries, with ligature of all arteries very close to the aorta. After that, by synchronous endovascular technique a complete aneurysmal exclusion of thoracoabdominal aneurysm with thoracic stent-graft was performed. The postoperative course was conducted properly and the patient left the Clinic for Vascular Surgery on postoperative day 21. Control CT, performed 3 months after the surgery

  13. Expression and secretion of Salmonella pathogenicity island-2 virulence genes in response to acidification exhibit differential requirements of a functional type III secretion apparatus and SsaL.

    Science.gov (United States)

    Coombes, Brian K; Brown, Nat F; Valdez, Yanet; Brumell, John H; Finlay, B Brett

    2004-11-26

    Salmonella pathogenicity island (SPI)-2 is pivotal to the intracellular survival of Salmonella and for virulence in mammals. SPI-2 encodes virulence factors (called effectors) that are translocated into the host cell, a type III secretion apparatus and a two-component regulatory system that regulates intracellular expression of SPI-2. Salmonella SPI-2 secretion activity appears to be induced in response to acidification of the vacuole in which it replicates. Here we show that the expression of the SPI-2 proteins, SseB and SseD (filament and pore forming components of the secretion apparatus, respectively) in response to acidification requires an intact secretion system and SsaL, a Salmonella homologue of SepL, a regulator required for type III-dependent secretion of translocators but not effectors in attaching and effacing gastrointestinal pathogens. We show that the expression of SPI-2-encoded effectors is acid-regulated but can be uncoupled from the expression of filament and translocon components, thus showing a differential requirement of SsaL for expression. The secretion and translocation of SPI-2-encoded effectors requires SsaL, but SsaL is dispensable for the secretion of SPI-2 effectors encoded in other pathogenicity loci, suggesting a secretion regulation function for SsaL. Further, we demonstrate that the differential expression of adjacent genes within the sseA operon (sseD and sseE) occurs at the transcriptional level. These data indicate that a Salmonella SPI-2 activation state is achieved by an acidregulated response that requires SsaL. These data also suggest the existence of a previously unrecognized regulatory element within SPI-2 for the "effector operon" region downstream of sseD that might demarcate the expression of translocators and effectors.

  14. Exercise intolerance in Glycogen Storage Disease Type III

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Pradel, Agnès; Husu, Edith;

    2013-01-01

    Myopathic symptoms in Glycogen Storage Disease Type IIIa (GSD IIIa) are generally ascribed to the muscle wasting that these patients suffer in adult life, but an inability to debranch glycogen likely also has an impact on muscle energy metabolism. We hypothesized that patients with GSD IIIa can...... experience exercise intolerance due to insufficient carbohydrate oxidation in skeletal muscle. Six patients aged 17-36-years were studied. We determined VO 2peak (peak oxygen consumption), the response to forearm exercise, and the metabolic and cardiovascular responses to cycle exercise at 70% of VO 2peak...... capacity was significantly reduced, and our results indicate that this was due to a block in muscle glycogenolytic capacity. Our findings suggest that the general classification of GSD III as a glycogenosis characterized by fixed symptoms related to muscle wasting should be modified to include dynamic...

  15. Type II and Type III Radio Bursts and their Correlation with Solar Energetic Proton Events

    CERN Document Server

    Winter, L M

    2015-01-01

    Using the Wind/WAVES radio observations from 2010-2013, we present an analysis of the 123 decametric-hectometric (DH) type II solar radio bursts during this period, the associated type III burst properties, and their correlation with solar energetic proton (SEP) properties determined from analysis of the Geostationary Operational Environmental Satellite (GOES) observations. We present a useful catalog of the type II burst, type III burst, Langmuir wave, and proton flux properties for these 123 events, which we employ to develop a statistical relationship between the radio properties and peak proton flux that can be used to forecast SEP events. We find that all SEP events with a peak > 10 MeV flux above 15 pfu are associated with a type II burst and virtually all SEP events, 92%, are also associated with a type III radio burst. Based on a principal component analysis, the radio burst properties that are most highly correlated with the occurrence of gradual SEP events and account for the most variance in the ra...

  16. Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

    OpenAIRE

    Fujioka Shinsuke; Sundal Christina; Wszolek Zbigniew K

    2013-01-01

    Abstract Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and...

  17. Antiviral Type I and Type III Interferon Responses in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Thomas Michiels

    2013-03-01

    Full Text Available The central nervous system (CNS harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i preventing neuroinvasion and infection of CNS cells; ii the identity of IFN-producing cells in the CNS; iii the antiviral activity of ISGs; and iv the activity of viral proteins of neurotropic viruses that target the IFN pathway.

  18. pKBuS13, a KPC-2-encoding plasmid from Klebsiella pneumoniae sequence type 833, carrying Tn4401b inserted into an Xer site-specific recombination locus.

    Science.gov (United States)

    Garbari, Luigi; Busetti, Marina; Dolzani, Lucilla; Petix, Vincenzo; Knezevich, Anna; Bressan, Raffaela; Gionechetti, Fabrizia; Tonin, Enrico A; Lagatolla, Cristina

    2015-09-01

    Here, we report the first detection of a Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing Klebsiella pneumoniae strain belonging to sequence type 833 (ST833), collected in an Italian hospital from a patient coming from South America. Its bla KPC determinant was carried by a ColE1 plasmid, pKBuS13, that showed the Tn4401b::bla KPC-2 transposon inserted into the regulatory region of an Xer site-specific recombination locus. This interfered with the correct resolution of plasmid multimers into monomers, lowering plasmid stability and leading to overestimation of the number of plasmids harbored by a single host cell. Sequencing of the fragments adjacent to Tn4401b detected a region that did not have significant matches in databases other than the genome of a carbapenem-resistant Escherichia coli strain collected during the same year at a hospital in Boston. This is interesting in an epidemiologic context, as it suggests that despite the absence of tra genes and the instability under nonselective conditions, the circulation of pKBuS13 or of analogous plasmids might be wider than reported. PMID:26077252

  19. Functional Activation of the Flagellar Type III Secretion Export Apparatus.

    Directory of Open Access Journals (Sweden)

    Andrew M Phillips

    2015-08-01

    Full Text Available Flagella are assembled sequentially from the inside-out with morphogenetic checkpoints that enforce the temporal order of subunit addition. Here we show that flagellar basal bodies fail to proceed to hook assembly at high frequency in the absence of the monotopic protein SwrB of Bacillus subtilis. Genetic suppressor analysis indicates that SwrB activates the flagellar type III secretion export apparatus by the membrane protein FliP. Furthermore, mutants defective in the flagellar C-ring phenocopy the absence of SwrB for reduced hook frequency and C-ring defects may be bypassed either by SwrB overexpression or by a gain-of-function allele in the polymerization domain of FliG. We conclude that SwrB enhances the probability that the flagellar basal body adopts a conformation proficient for secretion to ensure that rod and hook subunits are not secreted in the absence of a suitable platform on which to polymerize.

  20. Radiative Type III Seesaw Model and its collider phenomenology

    CERN Document Server

    von der Pahlen, Federico; Restrepo, Diego; Zapata, Oscar

    2016-01-01

    We analyze the present bounds of a scotogenic model, the Radiative Type III Seesaw (RSIII), in which an additional scalar doublet and at least two fermion triplets of $SU(2)_L$ are added to the Standard Model (SM). In the RSIII the new physics (NP) sector is odd under an exact global $Z_2$ symmetry. This symmetry guaranties that the lightest NP neutral particle is stable, providing a natural dark matter (DM) candidate, and leads to naturally suppressed neutrino masses generated by a one-loop realization of an effective Weinberg operator. We focus on the region with the highest sensitivity in present and future LHC searches, with light scalar DM and at least one NP fermion triplet at the sub-TeV scale. This region allows for significant production cross-sections of NP fermion pairs at the LHC. We reinterpret a set of searches for supersymmetric particles at the LHC obtained using the package CheckMATE, to set limits on our model as a function of the masses of the NP particles and their Yukawa interactions. The...

  1. Small-Molecule Inhibitors of the Type III Secretion System

    Directory of Open Access Journals (Sweden)

    Lingling Gu

    2015-09-01

    Full Text Available Drug-resistant pathogens have presented increasing challenges to the discovery and development of new antibacterial agents. The type III secretion system (T3SS, existing in bacterial chromosomes or plasmids, is one of the most complicated protein secretion systems. T3SSs of animal and plant pathogens possess many highly conserved main structural components comprised of about 20 proteins. Many Gram-negative bacteria carry T3SS as a major virulence determinant, and using the T3SS, the bacteria secrete and inject effector proteins into target host cells, triggering disease symptoms. Therefore, T3SS has emerged as an attractive target for antimicrobial therapeutics. In recent years, many T3SS-targeting small-molecule inhibitors have been discovered; these inhibitors prevent the bacteria from injecting effector proteins and from causing pathophysiology in host cells. Targeting the virulence of Gram-negative pathogens, rather than their survival, is an innovative and promising approach that may greatly reduce selection pressures on pathogens to develop drug-resistant mutations. This article summarizes recent progress in the search for promising small-molecule T3SS inhibitors that target the secretion and translocation of bacterial effector proteins.

  2. Novel type III polyketide synthases from Aloe arborescens.

    Science.gov (United States)

    Mizuuchi, Yuusuke; Shi, She-Po; Wanibuchi, Kiyofumi; Kojima, Akiko; Morita, Hiroyuki; Noguchi, Hiroshi; Abe, Ikuro

    2009-04-01

    Aloe arborescens is a medicinal plant rich in aromatic polyketides, such as pharmaceutically important aloenin (hexaketide), aloesin (heptaketide) and barbaloin (octaketide). Three novel type III polyketide synthases (PKS3, PKS4 and PKS5) were cloned and sequenced from the aloe plant by cDNA library screening. The enzymes share 85-96% amino acid sequence identity with the previously reported pentaketide chromone synthase and octaketide synthase. Recombinant PKS4 and PKS5 expressed in Escherichia coli were functionally identical to octaketide synthase, catalyzing the sequential condensations of eight molecules of malonyl-CoA to produce octaketides SEK4/SEK4b. As in the case of octaketide synthase, the enzymes are possibly involved in the biosynthesis of the octaketide barbaloin. On the other hand, PKS3 is a multifunctional enzyme that produces a heptaketide aloesone (i.e. the aglycone of aloesin) as a major product from seven molecules of malonyl-CoA. In addition, PKS3 also afforded a hexaketide pyrone (i.e. the precursor of aloenin), a heptaketide 6-(2-acetyl-3,5-dihydroxybenzyl)-4-hydroxy-2-pyrone, a novel heptaketide 6-(2-(2,4-dihydroxy-6-methylphenyl)-2-oxoethyl)-4-hydroxy-2-pyrone and octaketides SEK4/SEK4b. This is the first demonstration of the enzymatic formation of the precursors of the pharmaceutically important aloesin and aloenin by a wild-type PKS obtained from A. arborescens. Interestingly, the aloesone-forming activity was maximum at 50 degrees C, and the novel heptaketide pyrone was non-enzymatically converted to aloesone. In PKS3, the active-site residue 207, which is crucial for controlling the polyketide chain length depending on the steric bulk of the side chain, is uniquely substituted with Ala. Site-directed mutagenesis demonstrated that the A207G mutant dominantly produced the octaketides SEK4/SEK4b, whereas the A207M mutant yielded a pentaketide 5,7-dihydroxy-2-methylchromone. PMID:19348024

  3. Synthesis of type III collagen by fibroblasts from the embryonic chick cornea

    OpenAIRE

    1980-01-01

    Synthesis of collagen types I, II, III, and IV in cells from the embryonic chick cornea was studied using specific antibodies and immunofluorescence. Synthesis of radioactively labeled collagen types I and III was followed by fluorographic detection of cyanogen bromide peptides on polyacrylamide slab gels and by carboxymethylcellulose chromatography followed by disc gel electrophoresis. Type III collagen had been detected previously by indirect immunofluorescence in the corneal epithelial cel...

  4. Harnessing type I and type III CRISPR-Cas systems for genome editing

    DEFF Research Database (Denmark)

    Li, Yingjun; Pan, Saifu; Zhang, Yan;

    2016-01-01

    CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems are widespread in archaea and bacteria, and research on their molecular mechanisms has led to the development of genome-editing techniques based on a few Type II systems. However, there has not been any...... report on harnessing a Type I or Type III system for genome editing. Here, a method was developed to repurpose both CRISPR-Cas systems for genetic manipulation in Sulfolobus islandicus, a thermophilic archaeon. A novel type of genome-editing plasmid (pGE) was constructed, carrying an artificial mini-CRISPR...... and selectively retained as transformants. Using this strategy, different types of mutation were generated, including deletion, insertion and point mutations. We envision this method is readily applicable to different bacteria and archaea that carry an active CRISPR-Cas system of DNA interference provided...

  5. A Possible Anticancer Agent, Type III Interferon, Activates Cell Death Pathways and Produces Antitumor Effects

    Directory of Open Access Journals (Sweden)

    Masatoshi Tagawa

    2011-01-01

    Full Text Available Recently identified interleukin-28 and -29 belong to a novel type III interferon (IFN family, which could have distinct biological properties from type I and II IFNs. Type I IFNs, IFN-α/β, have been clinically applied for treating a certain kind of malignancies for over 30 years, but a wide range of the adverse effects hampered the further clinical applications. Type III IFNs, IFN-λs, have similar signaling pathways as IFN-α/β and inhibits proliferation of tumor cells through cell cycle arrest or apoptosis. Restricted patterns of type III IFN receptor expression in contrast to ubiquitously expressed IFN-α/β receptors suggest that type III IFNs have limited cytotoxicity to normal cells and can be a possible anticancer agent. In this paper, we summarize the current knowledge on the IFN-λs-mediated tumor cell death and discuss the functional difference between type I and III IFNs.

  6. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

    Science.gov (United States)

    Georgy, Gehan S; Nassar, Noha N; Mansour, Hanaa A; Abdallah, Dalaal M

    2013-01-01

    Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-α and decreased insulin growth factor (IGF)-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and

  7. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Gehan S Georgy

    Full Text Available Cerebrolysin (CBL, a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF, is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i vehicle- (ii CBL- and (iii STZ diabetic-control as well as (iv STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%, which were associated by weight loss, elevated tumor necrosis factor (TNF-α and decreased insulin growth factor (IGF-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU, glycine, serotonin (5-HT and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti

  8. A note on tilted Bianchi type VIh models: the type III bifurcation

    Science.gov (United States)

    Coley, A. A.; Hervik, S.

    2008-10-01

    In this note we complete the analysis of Hervik, van den Hoogen, Lim and Coley (2007 Class. Quantum Grav. 24 3859) of the late-time behaviour of tilted perfect fluid Bianchi type III models. We consider models with dust, and perfect fluids stiffer than dust, and eludicate the late-time behaviour by studying the centre manifold which dominates the behaviour of the model at late times. In the dust case, this centre manifold is three-dimensional and can be considered a double bifurcation as the two parameters (h and γ) of the type VIh model are varied. We therefore complete the analysis of the late-time behaviour of tilted ever-expanding Bianchi models of types I VIII.

  9. Antiviral activity of bovine type III interferon against foot-and-mouth disease virus

    Science.gov (United States)

    Interferons (IFN) are the first line of defense against viral infections. Recently a new family of IFNs, type III, has been identified in humans, mice, swine and chickens. Here we report the identification and characterization of a member of the bovine type III IFN family, boIFN-lambda3, also known...

  10. Behind the lines–actions of bacterial type III effector proteins in plant cells

    Science.gov (United States)

    Büttner, Daniela

    2016-01-01

    Pathogenicity of most Gram-negative plant-pathogenic bacteria depends on the type III secretion (T3S) system, which translocates bacterial effector proteins into plant cells. Type III effectors modulate plant cellular pathways to the benefit of the pathogen and promote bacterial multiplication. One major virulence function of type III effectors is the suppression of plant innate immunity, which is triggered upon recognition of pathogen-derived molecular patterns by plant receptor proteins. Type III effectors also interfere with additional plant cellular processes including proteasome-dependent protein degradation, phytohormone signaling, the formation of the cytoskeleton, vesicle transport and gene expression. This review summarizes our current knowledge on the molecular functions of type III effector proteins with known plant target molecules. Furthermore, plant defense strategies for the detection of effector protein activities or effector-triggered alterations in plant targets are discussed. PMID:27526699

  11. Identification of a major GpVI-binding locus in human type III collagen

    OpenAIRE

    Jarvis, Gavin E.; Raynal, Nicolas; Langford, Jonathan P.; Onley, David J.; Andrews, Allen; Smethurst, Peter A; Farndale, Richard W.

    2008-01-01

    We have analyzed the adhesion of human and murine platelets, and of recombinant human and murine GpVI ectodomains, to synthetic triple-helical collagen-like peptides. These included 57 peptides derived from the sequence of human type III collagen and 9 peptides derived from the cyanogen bromide fragment of bovine type III collagen, α1(III)CB4. We have identified several peptides that interact with GpVI, in particular a peptide designated III-30 with the sequence GAOGLRGGAGPOGPEGGKGAAGPOGPO. B...

  12. Frontal Sinus Patency after Extended Frontal Sinusotomy Type III

    Science.gov (United States)

    Hajbeygi, Mansour; Nadjafi, Ali; Amali, Amin; Saedi, Babak; Sadrehosseini, Seyed Mousa

    2016-01-01

    Introduction: The surgical management of chronic frontal sinus disorders remains a challenge for rhinologists. The aim of this study was to evaluate the result of Draf III in a series of patients who underwent this procedure. Materials and Methods: Twenty patients were included in this study. Demographic data, history of prior surgery, asthma, aspirin sensitivity and Lund–Mackay score were recorded. A visual analog scale was used for frontal-related symptoms. Patients were followed for a mean duration of 17.5 months and the patency of the frontal sinus ostium was closely monitored. Results: Fifteen patients with chronic frontal sinusitis, two patients with mucoceles, two with malignancy, and one with osteoma underwent Draf III. The mean symptoms score significantly decreased from 5.9 to 3. No ostial closure was seen in the follow-up period. Among 15 patients with chronic frontal sinusitis, 12 had patent ostia of whom three had significant stenosis. All patients with mucocele and osteoma had patent ostia in the follow-up period but patients with sinonasal malignancy showed significant stenosis. Conclusion: Draf III frontal sinusotomy is successful in alleviating patient symptoms and the frontal sinus neo-ostium will remain patent in long-term follow-up of most patients. Revision surgery will be required in some cases, which seems to be related to the nature of the underlying chronic sinus diseases. PMID:27738610

  13. "Do Type III-associated escaping electron beams cool the corona?"

    Science.gov (United States)

    Saint-Hilaire, P.; Wang, L.; Vilmer, N.; Kerdraon, A.

    2012-12-01

    A recent study of decimetric Type III radio burst emission from data from the Nancay Radio Heliograph will be presented. It examined sizes, locations, and fluxes of close to 10'000 decimetric Type III bursts. The flux study suggests that electron beams related to Type III emission could be responsible for carrying energy away from the corona in a proportion similar to EUV nanoflares. This tentative conclusion was reached from comparing Type III dN/dS distributions to the dN/dS of EUV/SXR nano-/micro-flares. The biggest uncertainty is the radiative efficiency, i.e. the ratio of radiated energy in decimetric Type III bursts and the energy of the electrons in the beams associated with them. We will constrain this value through other, new observations: we have already computed the amount of Type III radiated energy from NRH observations, and we will now compare them with the amount of energy in the corresponding beam electron detected in-situ by the Wind spacecraft. Given our sample of close to 10'000 decimetric Type IIIs, we expect a decent amount of in-situ beam energy estimates from magnetically connected events. Moreover, we will compare with X-ray-derived energies from corresponding RHESSI (micro)flares, when such an association exists.

  14. Do Type III-associated Escaping Electron Beams Cool The Corona?

    Science.gov (United States)

    Saint-Hilaire, Pascal; Wang, L.; Christe, S. D.; Vilmer, N.; Kerdraon, A.; Lin, R. P.

    2012-05-01

    A recent study of decimetric Type III radio burst emission from data from the Nancay Radio Heliograph (NRH) will be presented. It examined sizes, locations, and fluxes of close to 10'000 decimetric Type III bursts. The flux study suggests that electron beams related to Type III emission could be responsible for carrying energy away from the corona in a proportion similar to that of EUV nanoflare heating. This tentative conclusion was reached from comparing Type III dN/dS distributions to the dN/dS of EUV/SXR nano-/micro-flares. The biggest uncertainty is the radiative efficiency, i.e. the ratio of radiated energy in decimetric Type III bursts and the energy of the electrons in the beams associated with them. We will constrain this value through other, new observations: we have already computed the amount of Type III radiated energy from NRH observations, and we will now compare them with the amount of energy in the corresponding beam electron detected in-situ by the Wind spacecraft. Given our sample of close to 10'000 decimetric Type IIIs, we expect a decent amount of in-situ beam energy estimates from magnetically connected events. Moreover, we will compare with X-ray-derived energies from corresponding RHESSI (micro)flares, when such an association exists.

  15. Effects of overinflation on procollagen type III expression in experimental acute lung injury

    OpenAIRE

    de Carvalho, Maria-Eudóxia Pilotto; Dolhnikoff, Marisa; Meireles, Sibele Inácio; Reis, Luiz Fernando Lima; Martins, Milton Arruda; Deheinzelin, Daniel

    2007-01-01

    Introduction In acute lung injury (ALI), elevation of procollagen type III (PC III) occurs early and has an adverse impact on outcome. We examined whether different high-inflation strategies of mechanical ventilation (MV) in oleic acid (OA) ALI alter regional expression of PC III. Methods We designed an experimental, randomized, and controlled protocol in which rats were allocated to two control groups (no injury, recruited [alveolar recruitment maneuver after tracheotomy without MV; n = 4 ra...

  16. Arnold-Chiari Malformation Type III With Meningoencephalocele: A Case Report

    OpenAIRE

    Jeong, Dae Ho; Kim, Chang Hwan.; Kim, Myeong Ok; Chung, Hyung; Kim, Tae Hyun; Jung, Han Young

    2014-01-01

    Arnold-Chiari malformation type III (CM III) is an extremely rare anomaly with poor prognosis. An encephalocele with brain anomalies as seen in CM II, and herniation of posterior fossa contents like the cerebellum are found in CM III. The female infant was a twin, born at 33 weeks, weighing 1.7 kg with a huge hydrocele on the craniocervical junction. After operations were performed, she was referred to the department of rehabilitation medicine for poor motor development, swallowing dysfunctio...

  17. Specific cleavage of human type III and IV collagens by Pseudomonas aeruginosa elastase.

    OpenAIRE

    Heck, L W; Morihara, K; McRae, W B; Miller, E J

    1986-01-01

    Purified Pseudomonas aeruginosa elastase cleaved human type III and IV collagens with the formation of specific cleavage products. Furthermore, type I collagen appeared to be slowly cleaved by both P. aeruginosa elastase and alkaline protease. These cleavage fragments from type III and IV collagens were separated from the intact collagen chains by SDS polyacrylamide gradient gel electrophoresis run under reducing conditions, and they were detected by their characteristic Coomassie blue staini...

  18. T3_MM: A Markov Model Effectively Classifies Bacterial Type III Secretion Signals

    OpenAIRE

    Yejun Wang; Ming'an Sun; Hongxia Bao; Aaron P. White

    2013-01-01

    MOTIVATION: Type III Secretion Systems (T3SSs) play important roles in the interaction between gram-negative bacteria and their hosts. T3SSs function by translocating a group of bacterial effector proteins into the host cytoplasm. The details of specific type III secretion process are yet to be clarified. This research focused on comparing the amino acid composition within the N-terminal 100 amino acids from type III secretion (T3S) signal sequences or non-T3S proteins, specifically whether e...

  19. Second harmonic generation microscopy differentiates collagen type I and type III in COPD

    Science.gov (United States)

    Suzuki, Masaru; Kayra, Damian; Elliott, W. Mark; Hogg, James C.; Abraham, Thomas

    2012-03-01

    The structural remodeling of extracellular matrix proteins in peripheral lung region is an important feature in chronic obstructive pulmonary disease (COPD). Multiphoton microscopy is capable of inducing specific second harmonic generation (SHG) signal from non-centrosymmetric structural proteins such as fibrillar collagens. In this study, SHG microscopy was used to examine structural remodeling of the fibrillar collagens in human lungs undergoing emphysematous destruction (n=2). The SHG signals originating from these diseased lung thin sections from base to apex (n=16) were captured simultaneously in both forward and backward directions. We found that the SHG images detected in the forward direction showed well-developed and well-structured thick collagen fibers while the SHG images detected in the backward direction showed striking different morphological features which included the diffused pattern of forward detected structures plus other forms of collagen structures. Comparison of these images with the wellestablished immunohistochemical staining indicated that the structures detected in the forward direction are primarily the thick collagen type I fibers and the structures identified in the backward direction are diffusive structures of forward detected collagen type I plus collagen type III. In conclusion, we here demonstrate the feasibility of SHG microscopy in differentiating fibrillar collagen subtypes and understanding their remodeling in diseased lung tissues.

  20. Critical behavior of the Lyapunov exponent in type-III intermittency

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez-Llamoza, O. [Departamento de Fisica, FACYT, Universidad de Carabobo, Valencia (Venezuela); Centro de Fisica Fundamental, Grupo de Caos y Sistemas Complejos, Universidad de Los Andes, Merida 5251, Merida (Venezuela)], E-mail: llamoza@ula.ve; Cosenza, M.G. [Centro de Fisica Fundamental, Grupo de Caos y Sistemas Complejos, Universidad de Los Andes, Merida 5251, Merida (Venezuela); Ponce, G.A. [Departamento de Fisica, Universidad Nacional Autonoma de Honduras (Honduras); Departamento de Ciencias Naturales, Universidad Pedagogica Nacional Francisco Morazan, Tegucigalpa (Honduras)

    2008-04-15

    The critical behavior of the Lyapunov exponent near the transition to robust chaos via type-III intermittency is determined for a family of one-dimensional singular maps. Critical boundaries separating the region of robust chaos from the region where stable fixed points exist are calculated on the parameter space of the system. A critical exponent {beta} expressing the scaling of the Lyapunov exponent is calculated along the critical curve corresponding to the type-III intermittent transition to chaos. It is found that {beta} varies on the interval 0 {<=} {beta} < 1/2 as a function of the order of the singularity of the map. This contrasts with earlier predictions for the scaling behavior of the Lyapunov exponent in type-III intermittency. The variation of the critical exponent {beta} implies a continuous change in the nature of the transition to chaos via type-III intermittency, from a second-order, continuous transition to a first-order, discontinuous transition.

  1. Dietary management in glycogen storage disease type III : what is the evidence?

    NARCIS (Netherlands)

    Derks, Terry G. J.; Smit, G. Peter A.

    2015-01-01

    In childhood, GSD type III causes relatively severe fasting intolerance, classically associated with ketotic hypoglycaemia. During follow up, history of (documented) hypoglycaemia, clinical parameters (growth, liver size, motor development, neuromuscular parameters), laboratory parameters (glucose,

  2. Expression pattern of neuregulin-1 type III during the development of the peripheral nervous system

    OpenAIRE

    Liang-liang Huang; Zhong-yang Liu; Jing-hui Huang; Zhuo-jing Luo

    2015-01-01

    Neuregulin-1 type III is a key regulator in Schwann cell proliferation, committing to a myelinating fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin-1 type III in the peripheral nervous system during developmental periods (such as the premyelinating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern ...

  3. Gemfibrozil in the treatment of resistant familial hypercholesterolaemia and type III hyperlipoproteinaemia.

    OpenAIRE

    Houlston, R; Quiney, J; Watts, G F; Lewis, B.

    1988-01-01

    The efficacy of gemfibrozil in the treatment of resistant familial hypercholesterolaemia and type III hyperlipoproteinaemia was evaluated in 26 individuals over a mean period of 16 months. In the untreated state both disorders are associated with a high frequency of coronary heart disease. In the former, gemfibrozil with a bile acid sequestrant reduced plasma cholesterol by 32%, an incremental decrease of 17% compared with sequestrant therapy alone. In type III, plasma cholesterol was reduced...

  4. OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria

    DEFF Research Database (Denmark)

    Huizing, Marjan; Dorward, Heidi; Ly, Lien;

    2010-01-01

    3-Methylglutaconic aciduria type III (3-MGCA type III), caused by recessive mutations in the 2-exon gene OPA3, is characterized by early-onset bilateral optic atrophy, later-onset extrapyramidal dysfunction, and increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Her...... in the mitochondrion rather than the peroxisome and implicate loss of OPA3A rather than gain of OPA3B in disease etiology....

  5. Propolis Modifies Collagen Types I and III Accumulation in the Matrix of Burnt Tissue

    OpenAIRE

    Pawel Olczyk; Grzegorz Wisowski; Katarzyna Komosinska-Vassev; Jerzy Stojko; Katarzyna Klimek; Monika Olczyk; Kozma, Ewa M.

    2013-01-01

    Wound healing represents an interactive process which requires highly organized activity of various cells, synthesizing cytokines, growth factors, and collagen. Collagen types I and III, serving as structural and regulatory molecules, play pivotal roles during wound healing. The aim of this study was to compare the propolis and silver sulfadiazine therapeutic efficacy throughout the quantitative and qualitative assessment of collagen types I and III accumulation in the matrix of burnt tissues...

  6. Expression pattern of neuregulin-1 type III during the development of the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Liang-liang Huang

    2015-01-01

    Full Text Available Neuregulin-1 type III is a key regulator in Schwann cell proliferation, committing to a myelinating fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin-1 type III in the peripheral nervous system during developmental periods (such as the premyelinating stage, myelinating stage and postmyelinating stage has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various developmental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunofluorescent staining. The expression of neuregulin-1 type III mRNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunofluorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating (from postnatal day 2 to postnatal day 5 and myelinating stage (from postnatal day 5 to postnatal day 10, but remained at a high level in the postmyelinating stage (after postnatal day 10.

  7. Expression pattern of neuregulin-1 type III during the development of the peripheral nervous system.

    Science.gov (United States)

    Huang, Liang-Liang; Liu, Zhong-Yang; Huang, Jing-Hui; Luo, Zhuo-Jing

    2015-01-01

    Neuregulin-1 type III is a key regulator in Schwann cell proliferation, committing to a myelinating fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin-1 type III in the peripheral nervous system during developmental periods (such as the premyelinating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various developmental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunofluorescent staining. The expression of neuregulin-1 type III mRNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunofluorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating (from postnatal day 2 to postnatal day 5) and myelinating stage (from postnatal day 5 to postnatal day 10), but remained at a high level in the postmyelinating stage (after postnatal day 10). PMID:25788922

  8. Expression pattern of neuregulin-1 type III during the development of the peripheral nervous system

    Institute of Scientific and Technical Information of China (English)

    Liang-liang Huang; Zhong-yang Liu; Jing-hui Huang; Zhuo-jing Luo

    2015-01-01

    Neuregulin-1 type III is a key regulator in Schwann cell proliferation, committing to a myelinat-ing fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin-1 type III in the peripheral nervous system during developmental periods (such as the premyelin-ating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various develop-mental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunolfuorescent staining. The expression of neuregulin-1 type III mRNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunolfuorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating (from postnatal day 2 to postnatal day 5) and myelinating stage (from postnatal day 5 to postnatal day 10), but remained at a high level in the postmyelinating stage (after postnatal day 10).

  9. 46 CFR 170.135 - Operating information for a vessel with Type III subdivision.

    Science.gov (United States)

    2010-10-01

    ... Operating Personnel § 170.135 Operating information for a vessel with Type III subdivision. (a) In addition to the information required in 46 CFR 170.110, the stability booklet of a passenger vessel with Type... 46 Shipping 7 2010-10-01 2010-10-01 false Operating information for a vessel with Type...

  10. Regulation of type III iodothyronine deiodinase expression in human cell lines

    NARCIS (Netherlands)

    M.H.A. Kester; G.G.J.M. Kuiper; R. Versteeg; T.J. Visser

    2006-01-01

    Type I iodothyronine deiodinase (D1) and type II iodothyronine deiodinase (D2) catalyze the activation of the prohormone T-4 to the active hormone T-3; type III iodothyronine deiodinase (D3) catalyzes the inactivation of T-4 and T-3. D3 is highly expressed in brain, placenta, pregnant uterus, and fe

  11. Structural and biochemical characterization of SrcA, a multi-cargo type III secretion chaperone in Salmonella required for pathogenic association with a host.

    Directory of Open Access Journals (Sweden)

    Colin A Cooper

    2010-02-01

    Full Text Available Many Gram-negative bacteria colonize and exploit host niches using a protein apparatus called a type III secretion system (T3SS that translocates bacterial effector proteins into host cells where their functions are essential for pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the bacterial cytosol, establishing protein interaction networks needed for effector translocation into host cells. In Salmonella enterica serovar Typhimurium, a T3SS encoded in a large genomic island (SPI-2 is required for intracellular infection, but the chaperone complement required for effector translocation by this system is not known. Using a reverse genetics approach, we identified a multi-cargo secretion chaperone that is functionally integrated with the SPI-2-encoded T3SS and required for systemic infection in mice. Crystallographic analysis of SrcA at a resolution of 2.5 A revealed a dimer similar to the CesT chaperone from enteropathogenic E. coli but lacking a 17-amino acid extension at the carboxyl terminus. Further biochemical and quantitative proteomics data revealed three protein interactions with SrcA, including two effector cargos (SseL and PipB2 and the type III-associated ATPase, SsaN, that increases the efficiency of effector translocation. Using competitive infections in mice we show that SrcA increases bacterial fitness during host infection, highlighting the in vivo importance of effector chaperones for the SPI-2 T3SS.

  12. The extracellular matrix of Gadus morhua muscle contains types III, V, VI and IV collagens in addition to type I

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline; Lawson, M.A.

    2005-01-01

    Confocal microscopy and immuno‐histochemistry were used to examine collagens in the extracellular matrix of cod Gadus morhua swimming muscle. In addition to the well known presence of type I fibrous collagen, types III and VI were also found in the myocommata and the endomysium. The beaded collagen...

  13. Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections

    Science.gov (United States)

    Balan, Murugabaskar; Tseng, Hsiang-Chi; McElrath, Constance; Smirnov, Sergey V.; Peng, Jianya; Yasukawa, Linda L.; Durbin, Russell K.; Durbin, Joan E.; Greenberg, Harry B.; Kotenko, Sergei V.

    2016-01-01

    Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain) and heterologous (non-murine) simian (RRV strain) rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI) tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but overlapping sets

  14. Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections.

    Directory of Open Access Journals (Sweden)

    Jian-Da Lin

    2016-04-01

    Full Text Available Type I (IFN-α/β and type III (IFN-λ interferons (IFNs exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain and heterologous (non-murine simian (RRV strain rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but

  15. Distinct Roles of Type I and Type III Interferons in Intestinal Immunity to Homologous and Heterologous Rotavirus Infections.

    Science.gov (United States)

    Lin, Jian-Da; Feng, Ningguo; Sen, Adrish; Balan, Murugabaskar; Tseng, Hsiang-Chi; McElrath, Constance; Smirnov, Sergey V; Peng, Jianya; Yasukawa, Linda L; Durbin, Russell K; Durbin, Joan E; Greenberg, Harry B; Kotenko, Sergei V

    2016-04-01

    Type I (IFN-α/β) and type III (IFN-λ) interferons (IFNs) exert shared antiviral activities through distinct receptors. However, their relative importance for antiviral protection of different organ systems against specific viruses remains to be fully explored. We used mouse strains deficient in type-specific IFN signaling, STAT1 and Rag2 to dissect distinct and overlapping contributions of type I and type III IFNs to protection against homologous murine (EW-RV strain) and heterologous (non-murine) simian (RRV strain) rotavirus infections in suckling mice. Experiments demonstrated that murine EW-RV is insensitive to the action of both types of IFNs, and that timely viral clearance depends upon adaptive immune responses. In contrast, both type I and type III IFNs can control replication of the heterologous simian RRV in the gastrointestinal (GI) tract, and they cooperate to limit extra-intestinal simian RRV replication. Surprisingly, intestinal epithelial cells were sensitive to both IFN types in neonatal mice, although their responsiveness to type I, but not type III IFNs, diminished in adult mice, revealing an unexpected age-dependent change in specific contribution of type I versus type III IFNs to antiviral defenses in the GI tract. Transcriptional analysis revealed that intestinal antiviral responses to RV are triggered through either type of IFN receptor, and are greatly diminished when receptors for both IFN types are lacking. These results also demonstrate a murine host-specific resistance to IFN-mediated antiviral effects by murine EW-RV, but the retention of host efficacy through the cooperative action by type I and type III IFNs in restricting heterologous simian RRV growth and systemic replication in suckling mice. Collectively, our findings revealed a well-orchestrated spatial and temporal tuning of innate antiviral responses in the intestinal tract where two types of IFNs through distinct patterns of their expression and distinct but overlapping sets

  16. Accumulation of properly folded human type III procollagen molecules in specific intracellular membranous compartments in the yeast Pichia pastoris

    OpenAIRE

    Keizer-Gunnink, [No Value; Vuorela, A; Myllyharju, J; Pihlajaniemi, T.; Kivirikko, KI; Veenhuis, M; Keizer-Gunnink, Ineke; Kivirikko, Kari I.

    2000-01-01

    It was recently reported that co-expression of the proal(III) chain of human type III procollagen with the subunits of human prolyl 4-hydroxylase in Pichia pastoris produces fully hydroxylated and properly folded recombinant type III procollagen molecules (Vuorela, A., Myllyharju, J., Nissi, R., Pihlajaniemi, T., Kivirikko, K.I., 1997. Assembly of human prolyl 4-hydroxylase and type III collagen in the yeast Pichia pastoris: formation of a stable enzyme tetramer requires coexpression with col...

  17. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats

    OpenAIRE

    Georgy, Gehan S.; Nassar, Noha N.; Mansour, Hanaa A.; Dalaal M. Abdallah

    2013-01-01

    Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect...

  18. Identification and characterization of a type III Trichomonas vaginalis virus in the protozoan pathogen Trichomonas vaginalis.

    Science.gov (United States)

    Bessarab, Irina N; Nakajima, Rui; Liu, Hsing-Wei; Tai, Jung-Hsiang

    2011-02-01

    A type III Trichomonas vaginalis virus, which may be involved in transcriptional regulation of the major surface protein gene P270 of the protozoan pathogen Trichomonas vaginalis, was purified and characterized in the present study. The complete 4844-base-pair complementary DNA sequence of the viral genome reveals overlapping cap and pol genes with a putative ribosomal frame-shifting signal within the overlap region. The type III virus is related more closely to the type II virus than to the type I virus in the sequence of its ribosomal frameshift signal and in its capsid protein. Phylogenetic analysis revealed that these viruses could be grouped in the same clade as a genus distantly related to other genera in the family Totiviridae. Virus-induced P270 gene expression was only evident in Trichomonas vaginalis cells infected with either a type II or type III virus, but not with a type I virus. These findings suggest that transcription of the P270 gene is likely regulated by viral factors common to type II and type III viruses and thus provides important information for future investigation of virus-host interactions.

  19. DISTRIBUTION OF COLLAGENS TYPE-I, TYPE-III AND TYPE-V IN THE PANCREAS OF RAT, DOG, PIG AND MAN

    NARCIS (Netherlands)

    VANDEIJNEN, JHM; VANSUYLICHEM, PTR; WOLTERS, GHJ; VANSCHILFGAARDE, R

    1994-01-01

    The presence of collagens type I, type III and type V was determined immunohistochemically in pancreatic tissue of rat, pig, dog and man. The reaction to anti-collagen type I is weak (pig, dog) or moderate (rat, man) in the peri-insular region and in the lobar, lobular and acinar septa, whereas the

  20. Solar type III radio bursts modulated by homochromous Alfvén waves

    International Nuclear Information System (INIS)

    Solar type III radio bursts and their production mechanisms have been intensively studied in both theory and observation and are believed to be the most important signatures of electron acceleration in active regions. Recently, Wu et al. proposed that the electron-cyclotron maser emission (ECME) driven by an energetic electron beam could be responsible for producing type III bursts and pointed out that turbulent Alfvén waves can greatly influence the basic process of ECME via the oscillation of these electrons in the wave fields. This paper investigates effects of homochromous Alfvén waves (HAWs) on ECME driven by electron beams. Our results show that the growth rate of the O-mode wave will be significantly modulated by HAWs. We also discuss possible application to the formation of fine structures in type III bursts, such as so-called solar type IIIb radio bursts.

  1. OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria

    DEFF Research Database (Denmark)

    Huizing, Marjan; Dorward, Heidi; Ly, Lien;

    2010-01-01

    3-Methylglutaconic aciduria type III (3-MGCA type III), caused by recessive mutations in the 2-exon gene OPA3, is characterized by early-onset bilateral optic atrophy, later-onset extrapyramidal dysfunction, and increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Her...... we report the identification of a novel third OPA3 coding exon, the apparent product of a segmental duplication event, resulting in two gene transcripts, OPA3A and OPA3B. OPA3A deficiency (as in optic atrophy type 3) causes up-regulation of OPA3B. OPA3 protein function remains unknown......, but it contains a putative mitochondrial leader sequence, mitochondrial sorting signal and a peroxisomal sorting signal. Our green fluorescent protein tagged OPA3 expression studies found its localization to be predominantly mitochondrial. These findings thus place the cellular metabolic defect of 3-MGCA type III...

  2. Accumulation of properly folded human type III procollagen molecules in specific intracellular membranous compartments in the yeast Pichia pastoris

    NARCIS (Netherlands)

    Keizer-Gunnink, [No Value; Vuorela, A; Myllyharju, J; Pihlajaniemi, T; Kivirikko, KI; Veenhuis, M; Keizer-Gunnink, Ineke; Kivirikko, Kari I.

    2000-01-01

    It was recently reported that co-expression of the proal(III) chain of human type III procollagen with the subunits of human prolyl 4-hydroxylase in Pichia pastoris produces fully hydroxylated and properly folded recombinant type III procollagen molecules (Vuorela, A., Myllyharju, J., Nissi, R., Pih

  3. Type III IFN receptor expression and functional characterisation in the pteropid bat, Pteropus alecto.

    Directory of Open Access Journals (Sweden)

    Peng Zhou

    Full Text Available Bats are rich reservoir hosts for a variety of viruses, many of which are capable of spillover to other susceptible mammals with lethal consequences. The ability of bats to remain asymptomatic to viral infection may be due to the rapid control of viral replication very early in the immune response through innate antiviral mechanisms. Type I and III interferons (IFNs represent the first line of defence against viral infection in mammals, with both families of IFNs present in pteropid bats. To obtain further insight into the type III IFN system in bats, we describe the characterization of the type III IFN receptor (IFNλR in the black flying fox, P. alecto with the characterization of IFNλR1 and IL10R2 genes that make up the type III IFN receptor complex. The bat IFNλR complex has a wide tissue distribution and at the cellular level, both epithelial and immune cells are responsive to IFN-λ treatment. Furthermore, we demonstrate that the bat IFNλR1 chain acts as a functional receptor. To our knowledge, this report represents the first description of an IFN receptor in any species of bat. The responsiveness of bat cells to IFN-λ support a role for the type III IFN system by epithelial and immune cells in bats.

  4. Type III polyketide synthase repertoire in Zingiberaceae: computational insights into the sequence, structure and evolution.

    Science.gov (United States)

    Mallika, Vijayanathan; Aiswarya, Girija; Gincy, Paily Thottathil; Remakanthan, Appukuttan; Soniya, Eppurathu Vasudevan

    2016-07-01

    Zingiberaceae or 'ginger family' is the largest family in the order 'Zingiberales' with more than 1300 species in 52 genera, which are mostly distributed throughout Asia, tropical Africa and the native regions of America with their maximum diversity in Southeast Asia. Many of the members are important spice, medicinal or ornamental plants including ginger, turmeric, cardamom and kaempferia. These plants are distinguished for the highly valuable metabolic products, which are synthesised through phenylpropanoid pathway, where type III polyketide synthase is the key enzyme. In our present study, we used sequence, structural and evolutionary approaches to scrutinise the type III polyketide synthase (PKS) repertoire encoded in the Zingiberaceae family. Highly conserved amino acid residues in the sequence alignment and phylogram suggested strong relationships between the type III PKS members of Zingiberaceae. Sequence and structural level investigation of type III PKSs showed a small number of variations in the substrate binding pocket, leading to functional divergence among these PKS members. Molecular evolutionary studies indicate that type III PKSs within Zingiberaceae evolved under strong purifying selection pressure, and positive selections were rarely detected in the family. Structural modelling and protein-small molecule interaction studies on Zingiber officinale PKS 'a representative from Zingiberaceae' suggested that the protein is comparatively stable without much disorder and exhibited wide substrate acceptance. PMID:27138283

  5. Twenty-Two-Year Follow-up of Pronation External Rotation Type III-IV (OTA Type C) Ankle Fractures: A Retrospective Cohort Study.

    NARCIS (Netherlands)

    Donken, C.C.M.A.; Verhofstad, M.H.J.; Edwards, M.J.R.; Laarhoven, C.J.H.M. van

    2012-01-01

    OBJECTIVE: : Long-term evaluation protocolled treatment of pronation external rotation (PER) type III-IV (OTA type C) ankle fractures. DESIGN: : Level III retrospective cohort study. SETTING: : Level I trauma center. PATIENTS: : A consecutive series of 98 patients with PER III-IV ankle fractures bet

  6. Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

    Directory of Open Access Journals (Sweden)

    Fujioka Shinsuke

    2013-01-01

    Full Text Available Abstract Autosomal Dominant Cerebellar Ataxia (ADCA Type III is a type of spinocerebellar ataxia (SCA classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments.

  7. The heliocentric radial variation of plasma oscillations associated with type III radio bursts

    Science.gov (United States)

    Gurnett, D. A.; Anderson, R. R.; Scarf, F. L.; Kurth, W. S.

    1978-01-01

    A survey is presented of all of the electron plasma oscillation events found to date in association with low-frequency type III solar radio bursts using approximately 9 years of observations from the Imp 6 and 8, Helios 1 and 2, and Voyager 1 and 2 spacecraft. Plasma oscillation events associated with type III radio bursts show a pronounced increase in both the intensity and the frequency of occurrence with decreasing heliocentric radial distance. This radial dependence explains why intense electron plasma oscillations are seldon observed in association with type III radio bursts at the orbit of the earth. Possible interpretations of the observed radial variation in the plasma oscillation intensity are considered.

  8. Laparoscopic Treatment of Type III Mirizzi Syndrome by T-Tube Drainage

    Science.gov (United States)

    Yetışır, Fahri; Şarer, Akgün Ebru; Acar, H. Zafer; Polat, Yılmaz; Osmanoglu, Gokhan; Aygar, Muhittin; Ciftciler, A. Erdinc; Parlak, Omer

    2016-01-01

    Mirizzi syndrome (MS) is an impacted stone in the cystic duct or Hartmann's pouch that mechanically obstructs the common bile duct. We would like to report laparoscopic treatment of type III MS. A 75-year-old man was admitted with the complaint of abdominal pain and jaundice. The patient was accepted as MS type III according to radiological imaging and intraoperative view. Laparoscopic subtotal cholecystectomy, extraction of impacted stone by opening anterior surface of dilated cystic duct and choledochus, and repair of this opening by using the remaining part of gallbladder over the T-tube drainage were performed in a patient with type III MS. Application of reinforcement suture over stump was done in light of the checking with oliclinomel N4 injection trough the T-tube. At the 18-month follow-up, he was symptom-free with normal liver function tests. PMID:27293947

  9. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity

    DEFF Research Database (Denmark)

    Ank, Nina; Iversen, Marie B; Bartholdy, Christina;

    2008-01-01

    Type III IFNs (IFN-lambda/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-lambda w...

  10. Conservative Management of Type III Dens in Dente Using Cone Beam Computed Tomography

    Directory of Open Access Journals (Sweden)

    K Pradeep

    2012-01-01

    Full Text Available Dens in dente, also known as dens invaginatus, dilated composite odontoma, or deep foramen caecum, is a developmental malformation that usually affects maxillary incisor teeth, particularly lateral incisors. It may occur in teeth anywhere within the jaws, other locations are comparatively rare. It can occur within both the crown and the root, although crown invaginations are more common. The use of cone beam computed tomography (CBCT is very helpful in endodontic diagnosis of complex anatomic variations. In this case we demonstrate the use of CBCT in the evaluation and endodontic management of a Type III dens in dente (Oehler′s Type III.

  11. Enzymatic formation of unnatural novel chalcone, stilbene, and benzophenone scaffolds by plant type III polyketide synthase.

    Science.gov (United States)

    Shi, She-Po; Wanibuchi, Kiyofumi; Morita, Hiroyuki; Endo, Kohei; Noguchi, Hiroshi; Abe, Ikuro

    2009-02-01

    A C(19) hexaketide stilbene and a C(21) heptaketide chalcone were synthesized by Aloe arborescens octaketide synthase (OKS), a plant-specific type III polyketide synthase (PKS). Remarkably, the C(21) chalcone-forming activity was dramatically increased in a structure-guided OKS N222G mutant that produces a C(20) decaketide SEK15 from 10 molecules of malonyl-CoA. The findings suggested further strategies for production of unnatural polyketides by combination of the precursor-directed biosynthesis and the structure-guided engineering of type III PKS. PMID:19123789

  12. The aminoterminal propeptide of type III procollagen. Studies on physiology and pathophysiology

    DEFF Research Database (Denmark)

    Jensen, L T

    1997-01-01

    The aim of the present study was to examine the physiological basis for the clinical use of serum PIIINP as a marker of the deposition rate of type III collagen. The assumption was that the serum concentration of PIIINP would reflect the turnover of type III collagen and thus directly reflect......-venous shunt in conscious pigs was developed. Double and triple isotope tracer techniques were used for kinetic studies in the animal model and in cultures of tubule cells. The rat model with the induction of granulation tissue was used to investigate catabolic states. The anabolic state was studied in humans...

  13. Concurrent Occurrence of Type II and Type III Endoleak of Abdominal Aortic Aneurysm Stent Graft: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyoung Su; Hong, Seong Sook; Kim, Jung Hoon; Kim, Yong Jae; Goo, Dong Erk; Kwon, Kui Hyang; Choi, Deuk Lin [Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    2009-12-15

    Endoleak is an important complication following stent grafts for abdominal aortic aneurysms. Here we describe ultrasonography findings in an 86-year-old man including doppler ultrasonography and CT scan in an unusual and interesting case of the concurrent occurrence of a type II endoleak that originated from the left accessory renal artery and a type III endoleak due to shaft fracture of the stent

  14. Effect of Immobilization on Insoluble Collagen Concentration and Type I and Type III Collagen Isoforms of Rat Soleus Muscle

    OpenAIRE

    Hibino, Itaru; Okita, Minoru; Inoue, Takayuki; Banno, Yasuhiro; Hoso, Masahiro

    2008-01-01

    Immobilization is often associated with decreased muscle elasticity. This condition is known as muscle contracture; however, the mechanism remains unclear. The purpose of this study was to clarify the mechanism governing muscle contracture in rat soleus muscle by identifying changes in ankle joint mobility, insoluble collagen concentration and type I and type III collagen isoforms following 1- and 3-week immobilizations. Following a 1-week immobilization, range of motion (ROM) of dorsiflexion...

  15. Type III interferon gene expression in response to influenza virus infection in chicken and duck embryonic fibroblasts.

    Science.gov (United States)

    Zhang, Zhijie; Zou, Tingting; Hu, Xiaotong; Jin, Hong

    2015-12-01

    Type III interferons (IFN-λs) comprise a group of newly identified antiviral cytokines that are functionally similar to type I IFNs and elicit first-line antiviral responses. Recently, type III IFNs were identified in several species; however, little information is available about type III IFNs in ducks. We compared the expression of type III IFNs and their receptor in chicken embryonic fibroblasts (CEFs) and duck embryonic fibroblasts (DEFs) in response to influenza virus infection. The results showed that the expression of type III IFNs was upregulated in both DEFs and CEFs following infection with H1N1 influenza virus or treatment with poly (I:C), and expression levels were significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs (IL-28Rα) was also upregulated following infection with H1N1 virus or treatment with poly (I:C) and was significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs occurred from 8 hpi and remained at similar levels until 36 hpi in CEFs, but the expression level was elevated from 36 hpi in DEFs. These findings revealed the existence of distinct expression patterns for type III IFNs in chickens and ducks in response to influenza virus infection. The provided data are fundamentally useful in furthering our understanding of type III IFNs and innate antiviral responses in different species.

  16. Type III interferon gene expression in response to influenza virus infection in chicken and duck embryonic fibroblasts.

    Science.gov (United States)

    Zhang, Zhijie; Zou, Tingting; Hu, Xiaotong; Jin, Hong

    2015-12-01

    Type III interferons (IFN-λs) comprise a group of newly identified antiviral cytokines that are functionally similar to type I IFNs and elicit first-line antiviral responses. Recently, type III IFNs were identified in several species; however, little information is available about type III IFNs in ducks. We compared the expression of type III IFNs and their receptor in chicken embryonic fibroblasts (CEFs) and duck embryonic fibroblasts (DEFs) in response to influenza virus infection. The results showed that the expression of type III IFNs was upregulated in both DEFs and CEFs following infection with H1N1 influenza virus or treatment with poly (I:C), and expression levels were significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs (IL-28Rα) was also upregulated following infection with H1N1 virus or treatment with poly (I:C) and was significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs occurred from 8 hpi and remained at similar levels until 36 hpi in CEFs, but the expression level was elevated from 36 hpi in DEFs. These findings revealed the existence of distinct expression patterns for type III IFNs in chickens and ducks in response to influenza virus infection. The provided data are fundamentally useful in furthering our understanding of type III IFNs and innate antiviral responses in different species. PMID:26598110

  17. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase.

    Science.gov (United States)

    Austin, Michael B; Saito, Tamao; Bowman, Marianne E; Haydock, Stephen; Kato, Atsushi; Moore, Bradley S; Kay, Robert R; Noel, Joseph P

    2006-09-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two approximately 3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis. PMID:16906151

  18. A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle

    OpenAIRE

    Yao, Qing; Cui, Jixin; Zhu, Yongqun; Wang, Guolun; Hu, Liyan; Long, Chengzu; Cao, Ran; Liu, Xinqi; Huang, Niu; Chen, She; Liu, LiPing; Shao, Feng

    2009-01-01

    Pathogenic bacteria deliver effector proteins into host cells through the type III secretion apparatus to modulate the host function. We identify a family of proteins, homologous to the type III effector Cif from enteropathogenic Escherichia coli, in pathogens including Yersinia, Photorhabdus, and Burkholderia that contain functional type III secretion systems. Like Cif, this family of proteins is capable of arresting the host cell cycle at G2/M. Structure of one of the family members, Cif ho...

  19. Inhibition of type III radio emissions due to the interaction between two electron beams: Observations and simulations

    OpenAIRE

    Briand, C; Henri, P.; Hoang, S

    2014-01-01

    We report the peculiar interaction of two type III bursts observed in the solar wind. As electronbeams propagating on the same magnetic field lines cross, a spectacular depletion of the type III radioemission is observed. We combine observations from the WAVES experiment on board the STEREO missiontogether with kinetic plasma simulations to study the extinction of type III radio emission resulting fromthe interaction between two electron beams. The remote observations enable to follow the ele...

  20. On the speed and acceleration of electron beams triggering interplanetary type III radio bursts

    CERN Document Server

    Krupar, Vratislav; Soucek, Jan; Santolik, Ondrej; Maksimovic, Milan; Kruparova, Oksana

    2015-01-01

    Type III radio bursts are intense radio emissions triggered by beams of energetic electrons often associated with solar flares. These exciter beams propagate outwards from the Sun along an open magnetic field line in the corona and in the interplanetary (IP) medium. We performed a statistical survey of 29 simple and isolated IP type III bursts observed by STEREO/Waves instruments between January 2013 and September 2014. We investigated their time-frequency profiles in order to derive the speed and acceleration of exciter electron beams. We show these beams noticeably decelerate in the IP medium. Obtained speeds range from $\\sim$ 0.02c up to $\\sim$ 0.35c depending on initial assumptions. It corresponds to electron energies between tens of eV and hundreds of keV, and in order to explain the characteristic energies or speeds of type III electrons ($\\sim 0.1$c) observed simultaneously with Langmuir waves at 1 au, the emission of type III bursts near the peak should be predominately at double plasma frequency. Der...

  1. A bacterial pathogen uses distinct type III secretion systems to alternate between host kingdoms

    Science.gov (United States)

    Plant and animal-pathogenic bacteria utilize phylogenetically distinct type III secretion systems (T3SS) that produce needle-like injectisomes or pili for the delivery of effector proteins into host cells. Pantoea stewartii subsp. stewartii (Pnss), the causative agent of Stewart’s bacterial wilt and...

  2. Cloning and characterization of type III iodothyronine deiodinase from the fish Oreochromis niloticus

    NARCIS (Netherlands)

    J.P. Sanders; S. van der Geyten; E. Kaptein (Ellen); V.M. Darras (Veerle); E.R. Kuhn; J.L. Leonard; T.J. Visser (Ton)

    1999-01-01

    textabstractType III iodothyronine deiodinase (D3) catalyzes the inner ring deiodination (IRD) of T4 and T3 to the inactive metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2), respectively. Here we describe the cloning and characterization of complementary DNA (cDNA) co

  3. Anomalous Statistics for Type-III Intermittency in a 1D Map

    DEFF Research Database (Denmark)

    J., Laugesen; Carlsson, N.; Mosekilde, Erik;

    1997-01-01

    The statistics for the distribution of laminar phases in type-III intermittency is examined for a symmetric bimodal map. Due to a strongly nonuniform reinjection process, characteristic deviations from normal statistics are observed. There is an enhancement of relatively long laminar phases...

  4. Structure of Spa15, a type III secretion chaperone from Shigella flexneri with broad specificity

    NARCIS (Netherlands)

    Eerde, André van; Hamiaux, Cyril; Pérez, Javier; Parsot, Claude; Dijkstra, Bauke W.

    2004-01-01

    Type III secretion (TTS) systems are used by many Gram-negative pathogens to inject virulence proteins into the cells of their hosts. Several of these virulence effectors require TTS chaperones that maintain them in a secretion-competent state. Whereas most chaperones bind only one effector, Spa15 f

  5. Weapons of Mass Secretion : The Type III Secretion System of Shigella flexneri

    NARCIS (Netherlands)

    Sani, Musa

    2007-01-01

    In bacteria that are pathogenic for animals, type III secretion systems allow extracellular bacteria adhering to the surface of a host cell to inject specialized proteins across the plasma membrane. The injected proteins subvert the functioning of the aggressed cell or destroy its communications, fa

  6. Propolis Modifies Collagen Types I and III Accumulation in the Matrix of Burnt Tissue

    Directory of Open Access Journals (Sweden)

    Pawel Olczyk

    2013-01-01

    Full Text Available Wound healing represents an interactive process which requires highly organized activity of various cells, synthesizing cytokines, growth factors, and collagen. Collagen types I and III, serving as structural and regulatory molecules, play pivotal roles during wound healing. The aim of this study was to compare the propolis and silver sulfadiazine therapeutic efficacy throughout the quantitative and qualitative assessment of collagen types I and III accumulation in the matrix of burnt tissues. Burn wounds were inflicted on pigs, chosen for the evaluation of wound repair because of many similarities between pig and human skin. Isolated collagen types I and III were estimated by the surface plasmon resonance method with a subsequent collagenous quantification using electrophoretic and densitometric analyses. Propolis burn treatment led to enhanced collagens and its components expression, especially during the initial stage of the study. Less expressed changes were observed after silver sulfadiazine (AgSD application. AgSD and, with a smaller intensity, propolis stimulated accumulation of collagenous degradation products. The assessed propolis therapeutic efficacy, throughout quantitatively and qualitatively analyses of collagen types I and III expression and degradation in wounds matrix, may indicate that apitherapeutic agent can generate favorable biochemical environment supporting reepithelization.

  7. Liver transplantation for glycogen storage disease types I, III, and IV

    NARCIS (Netherlands)

    Matern, D; Starzl, TE; Arnaout, W; Barnard, J; Bynon, JS; Dhawan, A; Emond, J; Haagsma, EB; Hug, G; Lachaux, A; Smit, GPA; Chen, YT

    1999-01-01

    Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy hav

  8. IpaD is localized at the tip of the Shigella flexneri type III secretion apparatus

    NARCIS (Netherlands)

    Sani, Musa; Botteaux, Anne; Parsot, Claude; Sansonetti, Philippe; Boekema, Egbert J.; Allaoui, Abdelmounaaïm

    2007-01-01

    Type III secretion (T3S) systems are used by numerous Gram-negative pathogenic bacteria to inject virulence proteins into animal and plant host cells. The core of the T3S apparatus, known as the needle complex, is composed of a basal body transversing both bacterial membranes and a needle protruding

  9. Bartter syndrome Type III and congenital anomalies of the kidney and urinary tract: an antenatal presentation

    NARCIS (Netherlands)

    Westland, R.; Hack, W.W.; Horst, H.J. van der; Uittenbogaard, L.B.; Hagen, J.M. van; Valk, P. van der; Kamsteeg, E.J.; Heuvel, L.P. van den; Wijk, J.A. van

    2012-01-01

    Bartter syndrome encompasses a variety of inheritable renal tubular transport disorders characterized by hypokalemia and hypochloremic metabolic alkalosis. Bartter syndrome Type III is caused by genetic alterations in the chloride channel kidney B (CLCNKB) gene and often presents in the first 2 year

  10. Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria.

    Science.gov (United States)

    Tomoeda, K; Awata, H; Matsuura, T; Matsuda, I; Ploechl, E; Milovac, T; Boneh, A; Scott, C R; Danks, D M; Endo, F

    2000-11-01

    The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction of 4-hydroxyphenylpyruvic acid to homogentisic acid in the tyrosine catabolism pathway. A deficiency in the catalytic activity of HPD may lead to tyrosinemia type III, an autosomal recessive disorder characterized by elevated levels of blood tyrosine and massive excretion of tyrosine derivatives into urine. It has been postulated that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency. Hawkinsin is a sulfur amino acid identified as (2-l-cystein-S-yl, 4-dihydroxycyclohex-5-en-1-yl)acetic acid. Patients with hawkinsinuria excrete this metabolite in their urine throughout their life, although symptoms of metabolic acidosis and tyrosinemia improve in the first year of life. We performed analyses of the HPD gene in a patient with tyrosinemia type III and two unrelated patients with hawkinsinuria. A homozygous missense mutation predicting an Ala to Val change at codon 268 (A268V) in the HPD gene was found in the patient with tyrosinemia type III. A heterozygous missense mutation predicting an Ala to Thr change at codon 33 (A33T) was found in the same HPD gene in the two patients with hawkinsinuria. These findings support the hypothesis that alterations in the structure and activity of HPD are causally related to two different metabolic disorders, tyrosinemia type III and hawkinsinuria.

  11. Biofilms and type III secretion are not mutually exclusive in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Mikkelsen, H; Bond, N J; Skindersoe, M E;

    2009-01-01

    and fast growth. Conversely, chronic infections are often associated with the biofilm mode of growth, low virulence and slow growth that resembles that of planktonic cells in stationary phase. Biofilm formation and type III secretion have been shown to be reciprocally regulated, and it has been suggested...

  12. Spatial analysis of solar type III events associated with narrow band spikes at metric wavelengths

    CERN Document Server

    Paesold, G; Klein, K L; Vilmer, N

    2001-01-01

    The spatial association of narrow band metric radio spikes with type III bursts is analyzed. The analysis addresses the question of a possible causal relation between the spike emission and the acceleration of the energetic electrons causing the type III burst. The spikes are identified by the Phoenix-2 spectrometer (ETH Zurich) from survey solar observations in the frequency range from 220 MHz to 530 MHz. Simultaneous spatial information was provided by the Nancay Radioheliograph (NRH) at several frequencies. Five events were selected showing spikes at one or two and type III bursts at two or more Nancay frequencies. The 3-dimensional geometry of the single events has been reconstructed by applying different coronal density models. As a working hypothesis it is assumed that emission at the plasma frequency or its harmonic is the responsible radiation process for the spikes as well as for the type III bursts. It has been found that the spike source location is consistent with the backward extrapolation of the...

  13. Hypervirulent Clone of Group B Streptococcus Serotype III Sequence Type 283, Hong Kong, 1993-2012.

    Science.gov (United States)

    Ip, Margaret; Ang, Irene; Fung, Kitty; Liyanapathirana, Veranja; Luo, Ming Jing; Lai, Raymond

    2016-10-01

    We describe a hypervirulent clone of group B Streptococcus serotype III, subtype 4, sequence type 283, that caused invasive disease with a predilection for meningitis in Hong Kong during 1993-2012. The organism is associated with high mortality and increased summer prevalence and is linked to diseased fish from freshwater fish farms. PMID:27648702

  14. Mutualistic co-evolution of type III effector genes in Sinorhizobium fredii and Bradyrhizobium japonicum.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Kimbrel

    2013-02-01

    Full Text Available Two diametric paradigms have been proposed to model the molecular co-evolution of microbial mutualists and their eukaryotic hosts. In one, mutualist and host exhibit an antagonistic arms race and each partner evolves rapidly to maximize their own fitness from the interaction at potential expense of the other. In the opposing model, conflicts between mutualist and host are largely resolved and the interaction is characterized by evolutionary stasis. We tested these opposing frameworks in two lineages of mutualistic rhizobia, Sinorhizobium fredii and Bradyrhizobium japonicum. To examine genes demonstrably important for host-interactions we coupled the mining of genome sequences to a comprehensive functional screen for type III effector genes, which are necessary for many Gram-negative pathogens to infect their hosts. We demonstrate that the rhizobial type III effector genes exhibit a surprisingly high degree of conservation in content and sequence that is in contrast to those of a well characterized plant pathogenic species. This type III effector gene conservation is particularly striking in the context of the relatively high genome-wide diversity of rhizobia. The evolution of rhizobial type III effectors is inconsistent with the molecular arms race paradigm. Instead, our results reveal that these loci are relatively static in rhizobial lineages and suggest that fitness conflicts between rhizobia mutualists and their host plants have been largely resolved.

  15. Propolis Modifies Collagen Types I and III Accumulation in the Matrix of Burnt Tissue.

    Science.gov (United States)

    Olczyk, Pawel; Wisowski, Grzegorz; Komosinska-Vassev, Katarzyna; Stojko, Jerzy; Klimek, Katarzyna; Olczyk, Monika; Kozma, Ewa M

    2013-01-01

    Wound healing represents an interactive process which requires highly organized activity of various cells, synthesizing cytokines, growth factors, and collagen. Collagen types I and III, serving as structural and regulatory molecules, play pivotal roles during wound healing. The aim of this study was to compare the propolis and silver sulfadiazine therapeutic efficacy throughout the quantitative and qualitative assessment of collagen types I and III accumulation in the matrix of burnt tissues. Burn wounds were inflicted on pigs, chosen for the evaluation of wound repair because of many similarities between pig and human skin. Isolated collagen types I and III were estimated by the surface plasmon resonance method with a subsequent collagenous quantification using electrophoretic and densitometric analyses. Propolis burn treatment led to enhanced collagens and its components expression, especially during the initial stage of the study. Less expressed changes were observed after silver sulfadiazine (AgSD) application. AgSD and, with a smaller intensity, propolis stimulated accumulation of collagenous degradation products. The assessed propolis therapeutic efficacy, throughout quantitatively and qualitatively analyses of collagen types I and III expression and degradation in wounds matrix, may indicate that apitherapeutic agent can generate favorable biochemical environment supporting reepithelization.

  16. Integrated scenario with type-III ELMy H-mode edge: extrapolation to ITER

    NARCIS (Netherlands)

    Rapp, J.; Corre, Y.; Andrew, Y.; M.R. de Baar,; Beurskens, M.; Brezinsek, S.; Brix, M.; Devaux, S.; Eich, T.; Felton, R.; Fundamenski, W.; Giroud, C.; Howell, D.; Huber, A.; Jachmich, S.; Joffrin, E.; Korotkov, A.; Matthews, G. F.; McDonald, D. C.; Meigs, A.; Monier-Garbet, P.; Morgan, P.; Nunes, I.; van Rooij, G. J.; Sauter, O.; Stamp, M. F.; Telesca, G.; de Vries, P. C.; Zagorski, R.

    2009-01-01

    One of the most severe problems for fusion reactors is the power load on the plasma facing components. The challenge is to develop operation scenarios, which combine sufficient energy confinement with benign heat loads to the plasma facing components. The radiative type-III ELMy H-mode seems a possi

  17. On the Energy Momentum in Bianchi Type I-III-V-VI0 Space-Time

    CERN Document Server

    Aygun, S; Tarhan, I; Aygun, Melis; Aygun, Sezgin; Tarhan, Ismail

    2006-01-01

    In this study, using the energy momentum definitions of Einstein, Moller, Bergmann-Thomson, Landau-Lifshitz and Papapetrou we compute the total energy-momentum distribution (due to matter and fields including gravitation) of the universe based on general Bianchi type I-III-V-VI(o) space-time and its transforms type I, III, V, VI(o) metrics, respectively. The energy-momentum densities are found exactly same for Einstein and Bergmann-Thomson definitions. The total energy and momentum is found to be zero for Bianchi types I and VI(o) space-times. These results are same as a previous works of Radinschi, Banerjee-Sen, Xulu and Aydogdu-Salti. Another point is that our study agree with previous works of Cooperstock-Israelit, Rosen, Johri et al.

  18. Dentin phosphoprotein gene locus is not associated with dentinogenesis imperfecta types II and III

    Energy Technology Data Exchange (ETDEWEB)

    MacDougall, M.; Zeichner-David, M.; Davis, A.; Slavkin, H. (Univ. of Southern California, Los Angeles (United States)); Murray, J. (Univ. of Iowa, Iowa City (United States)); Crall, M. (Ohio State Univ., Columbus (United States))

    1992-01-01

    Dentinogenesis imperfecta (DGI) is an autosomal dominant inherited dental disease which affects dentin production and mineralization. Genetic linkage studies have been performed on several multigeneration informative kindreds. These studies determined linkage between DGI types II and III and group-specific component (vitamin D-binding protein). This gene locus has been localized to the long arm of human chromosome 4 in the region 4q11-q21. Although this disease has been mapped to chromosome 4, the defective gene product is yet to be determined. Biochemical studies have suggested abnormal levels of dentin phosphoprotein (DPP) associated with DGI type II. This highly acidic protein is the major noncollagenous component of dentin, being solely expressed by the ectomesenchymal derived odontoblast cells of the tooth. The purpose of the present study was to establish whether DPP is associated with DGI types II and III, by using molecular biology techniques. The results indicated that DPP is not localized to any region of human chromosome 4, thus suggesting that the DPP gene is not directly associated with DGI type II or DGI type III. The data do not exclude the possibility that other proteins associated with DPP posttranslational modifications might be responsible for this genetic disease.

  19. Bianchi type-I, type-III and Kantowski-Sachs solutions in f( T) gravity

    Science.gov (United States)

    Rodrigues, M. E.; Kpadonou, A. V.; Rahaman, F.; Oliveira, P. J.; Houndjo, M. J. S.

    2015-06-01

    In the context of modified tele-parallel theory of gravity, we undertake cosmological anisotropic models and search for their solutions. Within a suitable choice of non-diagonal tetrads, the decoupled equations of motion are obtained for Bianchi-I, Bianchi-III and Kantowski-Sachs models, from which we obtain the correspondent solutions. By the way, energy density and pressures are also obtained, showing, as an important result, that our universe may live a quintessence like universe even while anisotropic models are considered.

  20. Dentin phosphoprotein compound mutation in dentin sialophosphoprotein causes dentinogenesis imperfecta type III.

    Science.gov (United States)

    Dong, Juan; Gu, TingTing; Jeffords, Leticia; MacDougall, Mary

    2005-01-30

    A rare compound mutation involving a 36 bp deletion and 18 bp insertion within exon 5 of the dentin sialophosphoprotein (DSPP) gene has been identified in a family with dentinogenesis imperfecta type III (DGI-III). The DSPP gene encodes two major tooth matrix proteins dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). DSPP mutations associated with DGI-III results in an in frame truncation of the serine aspartic acid triplet repeat found in DPP near the highly conserved carboxyl terminal region shortening the protein by six amino acids. Clinically this family presents with discolored amber opalescent teeth and severe attrition of the tooth structure. This study is the first report of a mutation within DPP associated with a genetic dentin disease. Our study indicates that DGI-III is allelic with some forms of DGI-II with and without progressive hearing loss and dentin dysplasia type II that have been shown to be caused by mutations within the DSP coding or signal peptide regions.

  1. A New Look at Type III Bursts and their Use as Coronal Diagnostics

    CERN Document Server

    Beltran, Samuel Tun; White, Stephen

    2015-01-01

    We present meter wave solar radio spectra of the highest spectrotemporal resolution achieved to date. The observations, obtained with the first station of the Long Wavelength Array (LWA1), show unprecedented detail of solar emissions across a wide bandwidth during a Type III/IIIb storm. Our flux calibration demonstrates that the LWA1 can detect Type III bursts much weaker than 1 SFU, much lower than previous observations, and that the distribution of fluxes in these bursts varies with frequency. The high sensitivity and low noise in the data provide strong constraints to models of this type of plasma emission. The continuous generation of electron beams in the corona revealed by the high density Type III storm is evidence for ubiquitous magnetic reconnection in the lower corona. Such an abundance of reconnection events not only contributes to the total coronal energy budget, but also provides an engine by which to form the populations of seed particles responsible for proton-rich solar energetic particle even...

  2. Hierarchical effector protein transport by the Salmonella Typhimurium SPI-1 type III secretion system.

    Directory of Open Access Journals (Sweden)

    Brit Winnen

    Full Text Available BACKGROUND: Type III secretion systems (TTSS are employed by numerous pathogenic and symbiotic bacteria to inject a cocktail of different "effector proteins" into host cells. These effectors subvert host cell signaling to establish symbiosis or disease. METHODOLOGY/PRINCIPAL FINDINGS: We have studied the injection of SipA and SptP, two effector proteins of the invasion-associated Salmonella type III secretion system (TTSS-1. SipA and SptP trigger different host cell responses. SipA contributes to triggering actin rearrangements and invasion while SptP reverses the actin rearrangements after the invasion has been completed. Nevertheless, SipA and SptP were both pre-formed and stored in the bacterial cytosol before host cell encounter. By time lapse microscopy, we observed that SipA was injected earlier than SptP. Computer modeling revealed that two assumptions were sufficient to explain this injection hierarchy: a large number of SipA and SptP molecules compete for transport via a limiting number of TTSS; and the TTSS recognize SipA more efficiently than SptP. CONCLUSIONS/SIGNIFICANCE: This novel mechanism of hierarchical effector protein injection may serve to avoid functional interference between SipA and SptP. An injection hierarchy of this type may be of general importance, allowing bacteria to precisely time the host cell manipulation by type III effectors.

  3. Apparent diffusion coefficient vale of the brain in patients with Gaucher's disease type II and type III

    Energy Technology Data Exchange (ETDEWEB)

    Abdel Razek, Ahmed Abdel Khalek; Abd El-Gaber, Nahed [Mansoura Faculty of Medicine, Department of Diagnostic Radiology, Mansoura (Egypt); Abdalla, Ahmed; Fathy, Abeer [Mansoura Faculty of Medicine, Department of Pediatric, Mansoura (Egypt); Azab, Ahmed [Mansoura Faculty of Medicine, Department of Neurology, Mansoura (Egypt); Rahman, Ashraf Abdel [Radiology Unit of Pediatric Hospital, Mansoura (Egypt)

    2009-11-15

    The aim of this work is to assess the usefulness of apparent diffusion coefficient (ADC) value of the brain for diagnosis of patients with Gaucher's disease type II and type III. Prospective study was conducted upon 13 patients (nine boys and four girls aged 8 months-14 years: mean 6.1 years) with Gaucher's disease type II and III and for age-matched control group (n = 13). Diffusion-weighted magnetic resonance imaging using a single-shot echo-planar imaging with a diffusion-weighted factor b of 0, 500, and 1,000 s/mm{sup 2} was done for all patients and volunteers. The ADC value was calculated in ten regions of the brain parenchyma and correlated with genotyping. There was significantly lower ADC value of the cortical frontal (P = 0.003), cortical temporal (P = 0.04), frontal subcortical white matter (P = 0.02), corticospinal tract (P = 0.001), cerebellum (P = 0.001), medulla (P = 0.002), and midbrain (P = 0.02) between patients and volunteers. There was significant difference in the ADC value of the frontal and temporal gray matter (P = 0.04 and 0.05, respectively) between patients with heterozygous and homozygous gene mutation. We concluded that ADC value is a new promising quantitative imaging parameter that can be used for the detection of brain abnormalities in patients with Gaucher's disease type II and type III and has a correlation with genotyping. (orig.)

  4. Propagation of energetic electrons from the corona into interplanetary space and type III radio emission

    CERN Document Server

    Breitling, F; Vocks, C

    2015-01-01

    During solar flares a large amount of electrons with energies greater than 20 keV is generated with a production rate of typically $10^{36}$ s$^{-1}$. A part of them is able to propagate along open magnetic field lines through the corona into interplanetary space. During their travel they emit radio radiation which is observed as type III radio bursts in the frequency range from 100 MHz down to 10 kHz by the WAVES radio spectrometer aboard the spacecraft WIND, for instance. From the drift rates of these bursts in dynamic radio spectra the radial propagation velocity $V_r$ of the type III burst exciting electrons is derived by employing a newly developed density model of the heliosphere. Calculations show that the radio radiation is emitted by electrons with different $V_r$ and therefore by different electrons of the initially produced electron distribution.

  5. Strongly radiating type-III ELMy H-mode in JET - an integrated scenario for ITER

    International Nuclear Information System (INIS)

    As solution to the problems of transient and steady state energy exhaust the type-III ELMy H-mode is proposed. In recent experiments at JET it has been demonstrated that with seeding of nitrogen a radiative power fraction of 95% can be achieved, reducing the steady state and transient heat flux to acceptable values. Though the confinement of these discharges is reduced as well. Nevertheless, the ITER operational domain for Q = 10 does foresee operation at confinement enhancement factors of H 98(y,2) ∼ 0.78 at higher plasma currents (I p = 17 MA). It has been demonstrated at JET that an integrated scenario with type-III ELMs is feasible

  6. Strongly radiating type-III ELMy H-mode in JET - an integrated scenario for ITER

    Energy Technology Data Exchange (ETDEWEB)

    Rapp, J. [Institut fuer Plasmaphysik, Forschungszentrum Juelich GmbH, EURATOM Association, TEC, 52425 Juelich (Germany)]. E-mail: juergen.rapp@jet.efda.org; Matthews, G.F. [UKAEA-Fusion Association, Culham Science Centre, Abingdon OX14 3EA, OXON (United Kingdom); Monier-Garbet, P. [Association EURATOM-CEA sur la Fusion Controlle, Cadarache, 13108 Saint-Paul-lez-Durance (France); Sartori, R. [EFDA, CSU-Garching, 85748 Garching (Germany); Corre, Y. [Association EURATOM-CEA sur la Fusion Controlle, Cadarache, 13108 Saint-Paul-lez-Durance (France); Eich, T. [Max-Planck Institut fuer Plasmaphysik, 85748 Garching (Germany); Felton, R. [UKAEA-Fusion Association, Culham Science Centre, Abingdon OX14 3EA, OXON (United Kingdom); Fundamenski, W. [UKAEA-Fusion Association, Culham Science Centre, Abingdon OX14 3EA, OXON (United Kingdom); Giroud, C. [UKAEA-Fusion Association, Culham Science Centre, Abingdon OX14 3EA, OXON (United Kingdom); Huber, A. [Institut fuer Plasmaphysik, Forschungszentrum Juelich GmbH, EURATOM Association, TEC, 52425 Juelich (Germany); Jachmich, S. [Institut fuer Plasmaphysik, Forschungszentrum Juelich GmbH, EURATOM Association, TEC, 52425 Juelich (Germany); Morgan, P. [UKAEA-Fusion Association, Culham Science Centre, Abingdon OX14 3EA, OXON (United Kingdom); O' Mullane, M. [UKAEA-Fusion Association, Culham Science Centre, Abingdon OX14 3EA, OXON (United Kingdom); Koslowski, H.R. [Institut fuer Plasmaphysik, Forschungszentrum Juelich GmbH, EURATOM Association, TEC, 52425 Juelich (Germany); Stamp, M. [UKAEA-Fusion Association, Culham Science Centre, Abingdon OX14 3EA, OXON (United Kingdom)

    2005-03-01

    As solution to the problems of transient and steady state energy exhaust the type-III ELMy H-mode is proposed. In recent experiments at JET it has been demonstrated that with seeding of nitrogen a radiative power fraction of 95% can be achieved, reducing the steady state and transient heat flux to acceptable values. Though the confinement of these discharges is reduced as well. Nevertheless, the ITER operational domain for Q = 10 does foresee operation at confinement enhancement factors of H {sub 98(y,2)} {approx} 0.78 at higher plasma currents (I {sub p} = 17 MA). It has been demonstrated at JET that an integrated scenario with type-III ELMs is feasible.

  7. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III.

    Science.gov (United States)

    Rüetschi, U; Cerone, R; Pérez-Cerda, C; Schiaffino, M C; Standing, S; Ugarte, M; Holme, E

    2000-06-01

    Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), the second enzyme in the tyrosine catabolic pathway. The enzyme deficiency results in an accumulation and increased excretion of tyrosine and phenolic metabolites. Only a few cases with the disorder have been described, and the clinical spectrum of the disorder is unknown. Reported patients have presented with mental retardation or neurological symptoms or have been picked up by neonatal screening. We have identified four presumed pathogenic mutations (two missense and two nonsense mutations) in the HPD gene in three unrelated families encompassing four homozygous individuals and one compound heterozygous individual with tyrosinemia type III. Furthermore, a number of polymorphic mutations have been identified in the HPD gene. No correlation of the severity of the mutation and enzyme deficiency and mental function has been found; neither do the recorded tyrosine levels correlate with the clinical phenotype.

  8. Stopping Frequency of Type III Solar Radio Bursts in Expanding Magnetic Flux Tubes

    CERN Document Server

    Reid, Hamish A S

    2015-01-01

    Understanding the properties of type III radio bursts in the solar corona and interplanetary space is one of the best ways to remotely deduce the characteristics of solar accelerated electron beams and the solar wind plasma. One feature of all type III bursts is the lowest frequency they reach (or stopping frequency). This feature reflects the distance from the Sun that an electron beam can drive the observable plasma emission mechanism. The stopping frequency has never been systematically studied before from a theoretical perspective. Using numerical kinetic simulations, we explore the different parameters that dictate how far an electron beam can travel before it stops inducing a significant level of Langmuir waves, responsible for plasma radio emission. We use the quasilinear approach to model self-consistently the resonant interaction between electrons and Langmuir waves in inhomogeneous plasma, and take into consideration the expansion of the guiding magnetic flux tube and the turbulent density of the in...

  9. On Maximum Likelihood Estimation for Left Censored Burr Type III Distribution

    Directory of Open Access Journals (Sweden)

    Navid Feroze

    2015-12-01

    Full Text Available Burr type III is an important distribution used to model the failure time data. The paper addresses the problem of estimation of parameters of the Burr type III distribution based on maximum likelihood estimation (MLE when the samples are left censored. As the closed form expression for the MLEs of the parameters cannot be derived, the approximate solutions have been obtained through iterative procedures. An extensive simulation study has been carried out to investigate the performance of the estimators with respect to sample size, censoring rate and true parametric values. A real life example has also been presented. The study revealed that the proposed estimators are consistent and capable of providing efficient results under small to moderate samples.

  10. Global Analysis of a Delayed Impulsive Lotka-Volterra Model with Holling III Type Functional Response

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2015-01-01

    Full Text Available A delayed impulsive Lotka-Volterra model with Holing III type functional response was established. With the help of Mawhin’s Continuation Theorem in coincidence degree theory, a sufficient condition is found for the existence of positive periodic solutions of the system under consideration. By applying the comparison theorem and constructing a suitable Lyapunov functional, the permanence and global attractivity of the model are proved. Two numerical simulations are also given to illustrate our main results.

  11. Type III Seesaw and Dark Matter in a Supersymmetric Left-Right Model

    CERN Document Server

    Borah, Debasish

    2009-01-01

    We propose a new supersymmetric left right model with Higgs doublets carrying odd B-L charge, higgs bidoublet and heavy Higgs triplets with zero B-L charge and a set of sterile neutrinos which are singlet under the gauge group. We show that spontaneous parity violation can be achieved naturally in this model and the neutrino masses arise from the so called type III seesaw mechanism. We also discuss the possible phenomenology in the context of neutrino masses and dark matter.

  12. Overactive bladder after female genital mutilation/cutting (FGM/C) type III.

    Science.gov (United States)

    Abdulcadir, Jasmine; Dällenbach, Patrick

    2013-01-01

    A 27-year-old Somali woman with type III a-b female genital mutilation/cutting, consulted because of slow micturition, voiding efforts, urgency and urge incontinence (overactive bladder). She also referred primary dysmenorrhoea and superficial dyspareunia making complete sexual intercourses impossible. We treated her by defibulation and biofeedback re-educative therapy. We also offered a multidisciplinary counselling. At 5 months follow-up, urgency and urge incontinence had resolved and she became pregnant. PMID:24096069

  13. Developmental Defects in a Caenorhabditis elegans Model for Type III Galactosemia

    OpenAIRE

    Brokate-Llanos, Ana M.; Monje, José M.; Murdoch, Piedad del Socorro; Manuel J. Muñoz

    2014-01-01

    Type III galactosemia is a metabolic disorder caused by reduced activity of UDP-galactose-4-epimerase, which participates in galactose metabolism and the generation of various UDP-sugar species. We characterized gale-1 in Caenorhabditis elegans and found that a complete loss-of-function mutation is lethal, as has been hypothesized for humans, whereas a nonlethal partial loss-of-function allele causes a variety of developmental abnormalities, likely resulting from the impairment of the glycosy...

  14. Type III IFN Receptor Expression and Functional Characterisation in the Pteropid Bat, Pteropus alecto

    OpenAIRE

    Peng Zhou; Chris Cowled; Marsh, Glenn A.; Zhengli Shi; Lin-Fa Wang; Baker, Michelle L

    2011-01-01

    Bats are rich reservoir hosts for a variety of viruses, many of which are capable of spillover to other susceptible mammals with lethal consequences. The ability of bats to remain asymptomatic to viral infection may be due to the rapid control of viral replication very early in the immune response through innate antiviral mechanisms. Type I and III interferons (IFNs) represent the first line of defence against viral infection in mammals, with both families of IFNs present in pteropid bats. To...

  15. High frequency ion sound waves associated with Langmuir waves in type III radio burst source regions

    OpenAIRE

    G. Thejappa; Macdowall, R. J.

    2004-01-01

    Short wavelength ion sound waves (2-4kHz) are detected in association with the Langmuir waves (~15-30kHz) in the source regions of several local type III radio bursts. They are most probably not due to any resonant wave-wave interactions such as the electrostatic decay instability because their wavelengths are much shorter than those of Langmuir waves. The Langmuir waves occur as coherent field structures with peak intensities exceeding the Langm...

  16. New Tetrachromic VOF Stain (Type III-G.S) for Normal and Pathological Fish Tissues

    OpenAIRE

    Sarasquete, C.; Gutiérrez, M.

    2005-01-01

    A new VOF Type III-G.S stain was applied to histological sections of different organs and tissues of healthy and pathological larvae, juvenile and adult fish species (Solea senegalensis; Sparus aurata; Diplodus sargo; Pagrus auriga; Argyrosomus regius and Halobatrachus didactylus). In comparison to the original Gutiérrez VOF stain, more acid dyes of contrasting colours and polychromatic/metachromatic properties were incorporated as essential constituents of the tetrachromic VOF stain. This fa...

  17. Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III.

    Science.gov (United States)

    D'Eufemia, Patrizia; Finocchiaro, Roberto; Celli, Mauro; Raccio, Ivana; Properzi, Enrico; Zicari, Alessandra

    2009-06-01

    Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPD). Few cases have been described with mental retardation or neurological symptoms. Recently it has been demonstrated that 4-HPD participates to nitric oxide (NO) intracellular sequestration in Pseudomonas aeruginosa. 4-HPD is an ubiquitous enzyme with a prominent expression in neutrophils and neurons. In the nervous system NO has been perceived to be a potential neuromodulator although prolonged excessive generation is detrimental. We analyzed NO release by neutrophils of a patient with tyrosinemia type III in order to evaluate a possible influence of 4-HPD deficiency on this process. Our patient, previously described, is a 30-year-old women with persistent tyrosinemia (450-680 micromol/l) and deficient activity of 4-HPD. At 17 months of age she experienced an acute ataxia and drowsiness lasting for 10 days, but further clinical course showed persistent tyrosinemia with normal growth and psychomotor development. Neutrophils isolated from our patient exhibited a NO release greatly higher in respect to the controls (mean+/-SEM 23.2+/-1.8 micromol/10(6) cells vs 3.5+/-0.5 micromol/10(6) cells). Clinical findings of tyrosinemia type III include neurological symptoms and mental retardation but no consistent phenotype has emerged. Therefore the pathogenesis of neurological involvement is yet not well understood. Our results suggest that an excessive neutrophils of NO release could reflect the lack of scavenging action of 4-HPD. Considering the prominent expression of this enzyme in neurons, we hypothesize that excessive NO release could participate in neuronal damage explaining the neurological involvement described in patients with tyrosinemia type III.

  18. Deposition and degradation of C3 on type III group B streptococci.

    OpenAIRE

    Campbell, J R; Baker, C J; Edwards, M S

    1991-01-01

    Antibody to the polysaccharide capsule of type III group B streptococci (GBS) and complement are essential to host defense against systemic infection in neonates. Interactions between C3 degradation products and specific neutrophil receptors mediate the attachment and ingestion of these organisms. To evaluate the influence of capsule on C3 disposition, we compared the C3 fragments released from a highly encapsulated clinical isolate (M861) with those from an unencapsulated mutant (COH 31-15) ...

  19. A decade of solar Type III radio bursts observed by the Nancay Radioheliograph 1998-2008

    CERN Document Server

    Saint-Hilaire, Pascal; Kerdraon, Alain

    2012-01-01

    We present a statistical survey of almost 10 000 radio Type III bursts observed by the Nancay Radioheliograph from 1998 to 2008, covering nearly a full solar cycle. In particular, sources sizes, positions, and fluxes were examined. We find an east-west asymmetry in source positions which could be attributed to a 6(+/-)1 degree eastward tilt of the magnetic field, that source FWHM sizes s roughly follow a solar-cycle averaged distribution dN/ds = 14 {\

  20. Searching the charged Higgs boson of the type III two Higss doublet model

    CERN Document Server

    Cardenas, H

    2008-01-01

    In the framework of the Two Higgs Doublet Model (2HDM) type III appears two charged Higgs boson and recently there are experimental reports from D0 and CDF collaborations searching a particular signature of new physics. We present a review of the analisys done in the region $M_{H^+}>m_t$ by D0 collaboration and we use the ratio $R_\\sigma$ for the region $M_{H^+} < m_t$ in different scenarios of space parameter of this model.

  1. The relationship between chronic type III acromioclavicular joint dislocation and cervical spine pain

    Directory of Open Access Journals (Sweden)

    Vestri Anna R

    2009-12-01

    Full Text Available Abstract Background This study was aimed at evaluating whether or not patients with chronic type III acromioclavicular dislocation develop cervical spine pain and degenerative changes more frequently than normal subjects. Methods The cervical spine of 34 patients with chronic type III AC dislocation was radiographically evaluated. Osteophytosis presence was registered and the narrowing of the intervertebral disc and cervical lordosis were evaluated. Subjective cervical symptoms were investigated using the Northwick Park Neck Pain Questionnaire (NPQ. One-hundred healthy volunteers were recruited as a control group. Results The rate and distribution of osteophytosis and narrowed intervertebral disc were similar in both of the groups. Patients with chronic AC dislocation had a lower value of cervical lordosis. NPQ score was 17.3% in patients with AC separation (100% = the worst result and 2.2% in the control group (p Conclusions Our study shows that chronic type III AC dislocation does not interfere with osteophytes formation or intervertebral disc narrowing, but that it may predispose cervical hypolordosis. The higher average NPQ values were observed in patients with chronic AC dislocation, especially in those that developed cervical hypolordosis.

  2. HVEM serial-section analysis of rabbit foliate taste buds: I. Type III cells and their synapses.

    Science.gov (United States)

    Royer, S M; Kinnamon, J C

    1991-04-01

    Serially sectioned rabbit foliate taste buds were examined with high voltage electron microscopy (HVEM) and computer-assisted, three-dimensional reconstruction. This report focuses on the ultrastructure of the type III cells and their synapses with sensory nerve fibers. Type III cells have previously been proposed to be the primary gustatory receptor cells in taste buds of rabbits and other mammals. Within rabbit foliate taste buds, type III cells constitute a well-defined, easily recognizable class and are the only taste bud cells observed to form synapses with intragemmal nerve fibers. Among 18 type III cells reconstructed from serial sections, 11 formed from 1 to 6 synapses each with nerve fibers; 7 reconstructed type III cells formed no synapses. Examples of both convergence and divergence of synaptic input from type III cells onto nerve fibers were observed. The sizes of the active zones of the synapses and numbers of vesicles associated with the presynaptic membrane specializations were highly variable. Dense-cored vesicles 80-140 nm in diameter were often found among the 40-60 nm clear vesicles clustered at presynaptic sites. At some synapses, these large dense-cored vesicles appeared to be the predominant vesicle type. This observation suggests that there may be functionally different types of synapses in taste buds, distinguished by the prevalence of either clear or dense-cored vesicles. Previous investigations have indicated that the dense-cored vesicles in type III cells may be storage sites for biogenic amines.

  3. Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH

    DEFF Research Database (Denmark)

    Jensen, L T; Jørgensen, J O; Risteli, J;

    1991-01-01

    The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal...... propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days...... compared with 2 IU/day (normal replacement dose) (p = 0.04). Withdrawal of GH therapy for 14 days resulted in wider variation, but not significantly different from the levels at 2, 4 and 6 IU/day. A dose dependency was found regarding type III procollagen propeptide, showing significantly higher serum...

  4. Cross-reactivity to human T-lymphotropic virus type III/lymphadenopathy-associated virus and molecular cloning of simian T-cell lymphotropic virus type III from African green monkeys.

    OpenAIRE

    Hirsch, V.; Riedel, N.; Kornfeld, H; Kanki, P J; M Essex; Mullins, J I

    1986-01-01

    Simian T-lymphotropic retroviruses with structural, antigenic, and cytopathic features similar to the etiologic agent of human acquired immunodeficiency syndrome, human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), have been isolated from a variety of primate species including African green monkeys (STLV-IIIAGM). This report describes nucleic acid cross-reactivity between STLV-IIIAGM and HTLV-III/LAV, molecular cloning of the STLV-IIIAGM genome, and evaluation...

  5. First report on methicillin-resistant Staphylococcus aureus of Spa type T037, Sequence type 239, SCCmec type III/IIIA in Malaysia

    NARCIS (Netherlands)

    V. Neela (Vasanthakumari); H. Ghasemzadeh Moghaddam (Hamed); A.F. van Belkum (Alex); D. Horst-Kreft (Deborah); N.S. Mariana (Nor Shamsudin); E. Ghaznavi Rad (Ehsanollah)

    2010-01-01

    textabstractMethicillin-resistant Staphylococcus aureus (MRSA) from Malaysia were shown to possess staphylococcal cassette chromosome mec (SCCmec)-III and IIIA. Spa sequencing and multi-locus sequence typing (MLST) documented t037 and ST 239 (CC8) for 83.3% of the isolates. This confirms observation

  6. Hybrid H-mode scenario with nitrogen seeding and type III ELMs in JET

    Energy Technology Data Exchange (ETDEWEB)

    Corre, Y; Joffrin, E; Monier-Garbet, P; Arnoux, G; Hacquin, S; Imbeaux, F [CEA, IRFM, F-13108 Saint-Paul-lez-Durance (France); Andrew, Y; Beurskens, M; Brix, M; Buttery, R; Felton, R; Giroud, C; Kempenaars, M [EURATOM/UKAEA Association, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Brezinsek, S; Huber, A [Institut fuer Energieforschung-Plasmaphysik, Forschungszentrum Juelich, Association EURATOM-FZJ Trilateral Euregio Cluster (Germany); Coffey, I [Queen' s University, Belfast, BT7 1NN (United Kingdom); Crombe, K [Department of Applied Physics, Ghent University, Rozier 44, B-9000 Ghent (Belgium); De La Luna, E [EURATOM-CIEMAT, Laboratorio National de Fusion (Spain); Hobirk, J [Max-Planck-Institut fuer Plasmaphysik, EURATOM Association, Garching (Germany); Jachmich, S [Association EURATOM-Belgian State, KMS-ERM B-1000, Brussels (Belgium)], E-mail: yann.corre@cea.fr (and others)

    2008-11-15

    The performance of the 'hybrid' H-mode regime (long pulse operation with high neutron fluency) has been extensively investigated in JET during the 2005-2007 experimental campaign up to normalized pressure {beta}{sub N} = 3, toroidal magnetic field B{sub t} = 1.7 T, with type I ELMs plasma edge conditions. The optimized external current drive sources, self-generated non-inductive bootstrap current and plasma core stability properties provide a good prospect of achieving a high fusion gain at reduced plasma current for long durations in ITER. One of the remaining issues is the erosion of the divertor target plates associated with the type I ELM regime. A possible solution could be to operate with a plasma edge in the type III ELM regime (reduced transient and stationary heat loads) obtained with impurity seeding. An integrated hybrid type III ELM regime with a normalized pressure {beta}{sub N} = 2.6 (P{sub NBI} {approx} 20-22 MW) and a thermal confinement factor of H{sub 98}{sup *}(y,2){approx}0.83 has been recently successfully developed on JET with nitrogen seeding. This scenario shows good plasma edge condition (compatible with the future ITER-like wall on JET) and moderate MHD activity. In this paper, we report on the experimental development of the scenario (with plasma current I{sub p} = 1.7 MA and magnetic field B{sub t} = 1.7 T) and the trade-off between heat load reduction at the target plates and global confinement due to nitrogen seeding and type III ELM working conditions.

  7. Expression and Quorum Sensing Regulation of Type III Secretion System Genes of Vibrio harveyi during Infection of Gnotobiotic Brine Shrimp.

    Science.gov (United States)

    Ruwandeepika, H A Darshanee; Karunasagar, Indrani; Bossier, Peter; Defoirdt, Tom

    2015-01-01

    Type III secretion systems enable pathogens to inject their virulence factors directly into the cytoplasm of the host cells. The type III secretion system of Vibrio harveyi, a major pathogen of aquatic organisms and a model species in quorum sensing studies, is repressed by the quorum sensing master regulator LuxR. In this study, we found that during infection of gnotobiotic brine shrimp larvae, the expression levels of three type III secretion operons in V. harveyi increased within the first 12h after challenge and decreased again thereafter. The in vivo expression levels were highest in a mutant with a quorum sensing system that is locked in low cell density configuration (minimal LuxR levels) and lowest in a mutant with a quorum sensing system that is locked in the high cell density configuration (maximal LuxR levels), which is consistent with repression of type III secretion by LuxR. Remarkably, in vivo expression levels of the type III secretion system genes were much (> 1000 fold) higher than the in vitro expression levels, indicating that (currently unknown) host factors significantly induce the type III secretion system. Given the fact that type III secretion is energy-consuming, repression by the quorum sensing master regulators might be a mechanism to save energy under conditions where it does not provide an advantage to the cells. PMID:26636765

  8. Lack of the type III epidermal growth factor receptor mutation in colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Olsen, Dorte Aalund; Nielsen, Jens Nederby;

    2007-01-01

    BACKGROUND: Epidermal growth factor receptor (EGFR) analysis by traditional immunohistochemistry does not provide clinicians with a reliable tool for the selection of patients to EGFR-targeted treatment in colorectal cancer (CRC). Alternative methods and further understanding of the EGFR signaling...... network are being investigated and mutations in the EGFR gene have been identified. The type III epidermal growth factor receptor, a tumour-specific, ligand independent, constitutively activated form of EGFR, might contribute to the malignant phenotype in CRC and may be a potential target for anticancer...... therapy. The aim of the present study was to investigate the presence of EGFRvIII in CRC by PCR and protein analysis. MATERIALS AND METHODS: The study included 79 colorectal cancer patients for PCR analysis and 50 patients for protein analysis by Western blots, in two different laboratories. RESULTS...

  9. Management of Oehler’s Type III Dens Invaginatus Using Cone Beam Computed Tomography

    Directory of Open Access Journals (Sweden)

    Jaya Ranganathan

    2016-01-01

    Full Text Available Dens Invaginatus is a dental malformation that poses diagnostic difficulties in the clinical context. This anomaly may increase the risk of pulp disease and can potentially complicate endodontic procedure due to the aberrant root canal anatomy. Compared to conventional radiographs, three-dimensional images obtained with Cone Beam Computed Tomography (CBCT are invaluable in the diagnosis of the extent of this anomaly and in the appropriate treatment planning. Oehler’s classification (1957 for Dens Invaginatus (DI into three types depending on the depth of the invagination has been used for treatment planning. Of the three types Type III DI is characterized by infolding of the enamel into the tooth up to the root apex and is considered as the most severe variant of DI and hence the most challenging to treat endodontically, due to the morphological complexities. This report describes a case of Oehler’s Type III DI in a necrotic permanent maxillary lateral incisor in which CBCT images played a key role in diagnosis and treatment planning. The case was managed successfully by a combination of nonsurgical and surgical endodontic therapy with orthograde and retrograde thermoplastic gutta percha obturation.

  10. Analysis of the characteristics of patients with open tibial fractures of Gustilo and Anderson type III

    Directory of Open Access Journals (Sweden)

    Frederico Carlos Jaña Neto

    2016-04-01

    Full Text Available OBJECTIVE: To analyze the characteristics of patients with Gustilo-Anderson Type III open tibial fractures treated at a tertiary care hospital in São Paulo between January 2013 and August 2014. METHODS: This was a cross-sectional retrospective study. The following data were gathered from the electronic medical records: age; gender; diagnosis; trauma mechanism; comorbidities; associated fractures; Gustilo and Anderson, Tscherne and AO classifications; treatment (initial and definitive; presence of compartment syndrome; primary and secondary amputations; MESS (Mangled Extremity Severity Score index; mortality rate; and infection rate. RESULTS: 116 patients were included: 81% with fracture type IIIA, 12% IIIB and 7% IIIC; 85% males; mean age 32.3 years; and 57% victims of motorcycle accidents. Tibial shaft fractures were significantly more prevalent (67%. Eight patients were subjected to amputation: one primary case and seven secondary cases. Types IIIC (75% and IIIB (25% predominated among the patients subjected to secondary amputation. The MESS index was greater than 7 in 88% of the amputees and in 5% of the limb salvage group. CONCLUSION: The profile of patients with open tibial fracture of Gustilo and Anderson Type III mainly involved young male individuals who were victims of motorcycle accidents. The tibial shaft was the segment most affected. Only 7% of the patients underwent amputation. Given the current controversy in the literature about amputation or salvage of severely injured lower limbs, it becomes necessary to carry out prospective studies to support clinical decisions.

  11. Epigenetic reprogramming of the type III interferon response potentiates antiviral activity and suppresses tumor growth.

    Directory of Open Access Journals (Sweden)

    Siyuan Ding

    2014-01-01

    Full Text Available Type III interferon (IFN-λ exhibits potent antiviral activity similar to IFN-α/β, but in contrast to the ubiquitous expression of the IFN-α/β receptor, the IFN-λ receptor is restricted to cells of epithelial origin. Despite the importance of IFN-λ in tissue-specific antiviral immunity, the molecular mechanisms responsible for this confined receptor expression remain elusive. Here, we demonstrate that the histone deacetylase (HDAC repression machinery mediates transcriptional silencing of the unique IFN-λ receptor subunit (IFNLR1 in a cell-type-specific manner. Importantly, HDAC inhibitors elevate receptor expression and restore sensitivity to IFN-λ in previously nonresponsive cells, thereby enhancing protection against viral pathogens. In addition, blocking HDAC activity renders nonresponsive cell types susceptible to the pro-apoptotic activity of IFN-λ, revealing the combination of HDAC inhibitors and IFN-λ to be a potential antitumor strategy. These results demonstrate that the type III IFN response may be therapeutically harnessed by epigenetic rewiring of the IFN-λ receptor expression program.

  12. The type III secreted protein BspR regulates the virulence genes in Bordetella bronchiseptica.

    Directory of Open Access Journals (Sweden)

    Jun Kurushima

    Full Text Available Bordetella bronchiseptica is closely related with B. pertussis and B. parapertussis, the causative agents of whooping cough. These pathogenic species share a number of virulence genes, including the gene locus for the type III secretion system (T3SS that delivers effector proteins. To identify unknown type III effectors in Bordetella, secreted proteins in the bacterial culture supernatants of wild-type B. bronchiseptica and an isogenic T3SS-deficient mutant were compared with iTRAQ-based, quantitative proteomic analysis method. BB1639, annotated as a hypothetical protein, was identified as a novel type III secreted protein and was designated BspR (Bordetella secreted protein regulator. The virulence of a BspR mutant (ΔbspR in B. bronchiseptica was significantly attenuated in a mouse infection model. BspR was also highly conserved in B. pertussis and B. parapertussis, suggesting that BspR is an essential virulence factor in these three Bordetella species. Interestingly, the BspR-deficient strain showed hyper-secretion of T3SS-related proteins. Furthermore, T3SS-dependent host cell cytotoxicity and hemolytic activity were also enhanced in the absence of BspR. By contrast, the expression of filamentous hemagglutinin, pertactin, and adenylate cyclase toxin was completely abolished in the BspR-deficient strain. Finally, we demonstrated that BspR is involved in the iron-responsive regulation of T3SS. Thus, Bordetella virulence factors are coordinately but inversely controlled by BspR, which functions as a regulator in response to iron starvation.

  13. Type III Supracondylar Humerus Fractures in Children: Open Reduction and Pinning

    Directory of Open Access Journals (Sweden)

    Firat Ozan

    2016-04-01

    Full Text Available Aim: Supracondylar humerus fractures are the most common type of fractures involving the elbow region in children. Open reduction is a successful method for the management of displaced supracondylar fractures, with the most important advantages being complete anatomical reduction by visualising the fracture line and the lower level of risk for iatrogenic neurovascular injuries. In the present study, we assessed outcomes of open reduction and cross-pinning employed in the surgical management of paediatric Gartland type III supracondylar humerus fractures. Material and Method: The study included 18 children with Gartland extension type III supracondylar humerus fractures (13 boys, 5 girls; mean age: 7.3 ± 2.02 years; range, 3%u201312. There were fractures in the right elbows of 11 patients (61.1% and in the left elbows of seven (38.8%. The mean operative time was 53.3 ± 8.5 minutes (range, 45%u201370. The mean length of hospital stay was 1.7 ± 0.75 days (range, 1%u20133, while the mean follow-up time was 2.2 ± 0.6 years (range, 1.5%u20134. Results: According to the Flynn criteria, excellent results were obtained in six patients (33.3%, and good results in 12 (61.7% regarding changes in the carrying angle of the elbow. Functional assessment results were excellent for 14 patients (77.7% and good for four (22.3% regarding their loss of joint movement. Radiographic examinations revealed an average Baumann%u2019s angle of 75.6° (range, 70%u201385. Discussion: Good clinical outcomes can be achieved through the management of Gartland extension type III supracondylar humerus fractures using the open reduction technique. The most important disadvantage, however, is the post-surgical appearance of the elbow incision scar.

  14. Solution structure of monomeric BsaL, the type III secretion needle protein of Burkholderia pseudomallei.

    Science.gov (United States)

    Zhang, Lingling; Wang, Yu; Picking, Wendy L; Picking, William D; De Guzman, Roberto N

    2006-06-01

    Many gram-negative bacteria that are important human pathogens possess type III secretion systems as part of their required virulence factor repertoire. During the establishment of infection, these pathogens coordinately assemble greater than 20 different proteins into a macromolecular structure that spans the bacterial inner and outer membranes and, in many respects, resembles and functions like a syringe. This type III secretion apparatus (TTSA) is used to inject proteins into a host cell's membrane and cytoplasm to subvert normal cellular processes. The external portion of the TTSA is a needle that is composed of a single type of protein that is polymerized in a helical fashion to form an elongated tube with a central channel of 2-3 nm in diameter. TTSA needle proteins from a variety of bacterial pathogens share sequence conservation; however, no atomic structure for any TTSA needle protein is yet available. Here, we report the structure of a TTSA needle protein called BsaL from Burkholderia pseudomallei determined by nuclear magnetic resonance (NMR) spectroscopy. The central part of the protein assumes a helix-turn-helix core domain with two well-defined alpha-helices that are joined by an ordered, four-residue linker. This forms a two-helix bundle that is stabilized by interhelix hydrophobic contacts. Residues that flank this presumably exposed core region are not completely disordered, but adopt a partial helical conformation. The atomic structure of BsaL and its sequence homology with other TTSA needle proteins suggest potentially unique structural dynamics that could be linked with a universal mechanism for control of type III secretion in diverse gram-negative bacterial pathogens. PMID:16631790

  15. Complex Function for SicA, a Salmonella enterica Serovar Typhimurium Type III Secretion-Associated Chaperone

    OpenAIRE

    Tucker, Stephanie C.; Galán, Jorge E.

    2000-01-01

    Salmonella enterica encodes a type III secretion system within a pathogenicity island located at centisome 63 that is essential for virulence. All type III secretion systems require the function of a family of low-molecular-weight proteins that aid the secretion process by acting as partitioning factors and/or secretion pilots. One such protein is SicA, which is encoded immediately upstream of the type III secreted proteins SipB and SipC. We found that the absence of SicA results in the degra...

  16. Alterations in biosynthetic accumulation of collagen types I and III during growth and morphogenesis of embryonic mouse salivary glands

    Science.gov (United States)

    Hardman, P.; Spooner, B. S.

    1992-01-01

    We examined the biosynthetic patterns of interstitial collagens in mouse embryonic submandibular and sublingual glands cultured in vitro. Rudiments explanted on day 13 of gestation and cultured for 24, 48, and 72 h all synthesized collagen types I, III, and V. However, while the total incorporation of label into collagenous proteins did not change over the three-day culture period, the rate of accumulation of newly synthesized types I and III did change. At 24 h, the ratio of newly synthesized collagen types I:III was approximately 2, whereas at 72 h, the ratio was approximately 5. These data suggest that collagen types I and III may be important in initiation of branching in this organ, but that type I may become dominant in the later stages of development and in maintenance of the adult organ.

  17. Beat-type Langmuir wave emissions associated with a type III solar radio burst: Evidence of parametric decay

    Science.gov (United States)

    Hospodarsky, G. B.; Gurnett, D. A.

    1995-01-01

    Recent measurements from the plasma wave instrument on the Galileo spacecraft have shown that Langmuir waves observed in conjunction with a type III solar radio burst contain many beat-type waveforms, with beat frequencies ranging from about 150 to 650 Hz. Strong evidence exists that the beat pattern is produced by two closely spaced narrowband components. The most likely candidates for these two waves are a beam-generated Langmuir wave and an oppositely propagating Langmuir wave produced by parametric decay. In the parametric decay process, nonlinear interactions cause the beam-driven Langmuir wave to decay into a Langmuir wave and a low-frequency ion sound wave. Comparisons of the observed beat frequency are in good agreement with theoretical predictions for a three-wave parametric decay process. Weak low-frequency emissions are also sometimes observed at the predicted frequency of the ion sound wave.

  18. Trabecular Metal Augments for the Management of Paprosky Type III Defects Without Pelvic Discontinuity.

    Science.gov (United States)

    Grappiolo, Guido; Loppini, Mattia; Longo, Umile Giuseppe; Traverso, Francesco; Mazziotta, Giuseppe; Denaro, Vincenzo

    2015-06-01

    Fifty-five hips undergoing acetabular reconstruction with trabecular metal (TM)-coated cup and TM augments were reviewed at an average follow up of 53.7 months (36-91). Bony defects were Paprosky type IIIA in 42 and type IIIB without pelvic discontinuity in 13 hips. The average HHS increased from 40 (27-52) preoperatively to 90.5 (61-100) postoperatively (P<0.0001). Four (7.3%) of 55 hips underwent acetabular components revision: three cases of loosening (5.4%), and one of recurrent instability (1.8%) were reported. Survival rate at 2 and 5 years was 96.4% and 92.8%. In conclusion, the use of TM-coated cups and augments could be considered an effective management of Paprosky type III defects without pelvic discontinuity providing good clinical and radiographic outcomes in the mid term.

  19. Type-II/III DCT/DST algorithms with reduced number of arithmetic operations

    CERN Document Server

    Shao, Xuancheng

    2007-01-01

    We present algorithms for the discrete cosine transform (DCT) and discrete sine transform (DST), of types II and III, that achieve a lower count of real multiplications and additions than previously published algorithms, without sacrificing numerical accuracy. Asymptotically, the operation count is reduced from ~ 2N log_2 N to ~ (17/9) N log_2 N for a power-of-two transform size N. Furthermore, we show that a further N multiplications may be saved by a certain rescaling of the inputs or outputs, generalizing a well-known technique for N=8 by Arai et al. These results are derived by considering the DCT to be a special case of a DFT of length 4N, with certain symmetries, and then pruning redundant operations from a recent improved fast Fourier transform algorithm (based on a recursive rescaling of the conjugate-pair split radix algorithm). The improved algorithms for DCT-III, DST-II, and DST-III follow immediately from the improved count for the DCT-II.

  20. Type III procollagen N-terminal peptide (P-III-P), prolyl hydroxylase (PH), and laminin P sub 1 levels in serum and BALF of radiotherapy patients

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Shuichi (Komaki Municipal Hospital, Aichi (Japan)); Shindo, Jo; Horiba, Michiaki; Hara, Michihiro; Inoue, Koji

    1992-01-01

    The etiology of pulmonary fibrosis remains unclear, and at present there are no definite biochemical markers of its activity. We measured serum and BALF levels of type III procollagen N-terminal peptide (P-III-P), prolyl hydroxylase (PH), and laminin P{sub 1} in patients who had undergone radiotherapy for malignant neoplasms, and investigated their value as biochemical markers in a model of pulmonary fibrosis. The following results were obtained: 1) Patients with abnormal liver function had significantly higher serum P-III-P levels and showed a tendency to have higher serum PH levels. If P-III-P or PH are to be used as markers of pulmonary fibrosis, the effect of liver function must be taken into consideration; however, no significant difference was detected with respect to laminin P{sub 1} levels. 2) Serum P-III-P levels were significantly elevated by radiotherapy. 3) Laminin P{sub 1} levels rose in a similar manner to P-III-P levels after radiotherapy, but no significant change was detected. 4) In most cases, the levels of all markers in BALF were below the threshold of detection, nevertheless all three markers were elevated in a patient who developed diffuse radiation pneumonitis during radiotherapy. Increase in the lymphocyte count were found in BALF of this patient. 5) BALF hyaluronic acid levels were negative in the 3 cases assayed. 6) A significant correlation between P-III-P and laminin P{sub 1} in serum was shown, but no significant correlations could be found between the other combinations of markers in serum. Thus it appears that serum P-III-P and laminin P{sub 1} are valid biochemical markers of pulmonary fibrosis. It is expected that they will be useful for the detection of early radiation pneumonitis, the assessment of patients with pulmonary fibrosis, and the monitoring of steroid therapy. (author).

  1. Direct and Indirect Targeting of PP2A by Conserved Bacterial Type-III Effector Proteins

    OpenAIRE

    Lin Jin; Jong Hyun Ham; Rosemary Hage; Wanying Zhao; Jaricelis Soto-Hernández; Sang Yeol Lee; Seung-Mann Paek; Min Gab Kim; Charles Boone; Coplin, David L.; David Mackey

    2016-01-01

    Bacterial AvrE-family Type-III effector proteins (T3Es) contribute significantly to the virulence of plant-pathogenic species of Pseudomonas, Pantoea, Ralstonia, Erwinia, Dickeya and Pectobacterium, with hosts ranging from monocots to dicots. However, the mode of action of AvrE-family T3Es remains enigmatic, due in large part to their toxicity when expressed in plant or yeast cells. To search for targets of WtsE, an AvrE-family T3E from the maize pathogen Pantoea stewartii subsp. stewartii, w...

  2. Cloning and characterization of type III iodothyronine deiodinase from the fish Oreochromis niloticus

    OpenAIRE

    Sanders, J.P.; Van Der Geyten, S; Kaptein, Ellen; Darras, Veerle; Kuhn, E.R.; Leonard, J L; Visser, Ton

    1999-01-01

    textabstractType III iodothyronine deiodinase (D3) catalyzes the inner ring deiodination (IRD) of T4 and T3 to the inactive metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2), respectively. Here we describe the cloning and characterization of complementary DNA (cDNA) coding for D3 in fish (Oreochromis niloticus, tilapia). This cDNA contains 1478 nucleotides and codes for a protein of 267 amino acids, including a putative selenocysteine (Sec) residue, encoded by a TGA triplet, at position 131....

  3. The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK for critical steps in pathogenesis.

    LENUS (Irish Health Repository)

    Matlawska-Wasowska, Ksenia

    2010-12-01

    Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human host cell responses to V. parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance of MAPK activation for the ability of the bacterium to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.

  4. Pseudomonas aeruginosa uses type III secretion system to kill biofilm-associated amoebae

    DEFF Research Database (Denmark)

    Matz, Carsten; Moreno, Ana Maria; Alhede, Morten;

    2008-01-01

    should allow opportunistic pathogenic bacteria to utilize their eukaryote-targeting arsenal to attack and exploit protozoan host cells. Studying cocultures of the environmental pathogen Pseudomonas aeruginosa and the amoeba Acanthamoeba castellanii, we found that P. aeruginosa rapidly colonized...... and killed biofilm-associated amoebae by a quorum-sensing independent mechanism. Analysis of the amoeba-induced transcriptome indicated the involvement of the P. aeruginosa type III secretion system (T3SS) in this interaction. A comparison of mutants with specific defects in the T3SS demonstrated the use...

  5. Developmental defects in a Caenorhabditis elegans model for type III galactosemia.

    Science.gov (United States)

    Brokate-Llanos, Ana M; Monje, José M; Murdoch, Piedad Del Socorro; Muñoz, Manuel J

    2014-12-01

    Type III galactosemia is a metabolic disorder caused by reduced activity of UDP-galactose-4-epimerase, which participates in galactose metabolism and the generation of various UDP-sugar species. We characterized gale-1 in Caenorhabditis elegans and found that a complete loss-of-function mutation is lethal, as has been hypothesized for humans, whereas a nonlethal partial loss-of-function allele causes a variety of developmental abnormalities, likely resulting from the impairment of the glycosylation process. We also observed that gale-1 mutants are hypersensitive to galactose as well as to infections. Interestingly, we found interactions between gale-1 and the unfolded protein response. PMID:25298520

  6. Large scale simulations of solar type III radio bursts: flux density, drift rate, duration and bandwidth

    OpenAIRE

    Ratcliffe, H.; Kontar, E. P.; Reid, H. A. S.

    2014-01-01

    Non-thermal electrons accelerated in the solar corona can produce intense coherent radio emission, known as solar type III radio bursts. This intense radio emission is often observed from hundreds of MHz in the corona down to the tens of kHz range in interplanetary space. It involves a chain of physical processes from the generation of Langmuir waves to non-linear processes of wave-wave interaction. We develop a self-consistent model to calculate radio emission from a non-thermal electron pop...

  7. Serum type III procollagen peptide in asbestos workers: an early indicator of pulmonary fibrosis.

    OpenAIRE

    1988-01-01

    Serum type III procollagen peptide (PIIIP) concentrations were determined in 36 male workers exposed to asbestos fibres in the production of asbestos cement items and in 13 healthy male controls. Mean (SD) PIIIP serum concentrations were 9.3 (1.5) ng/ml (range 7-12) in the controls and 13.7 (3.5)ng/ml (range 7.5-20) in the asbestos workers; the difference was statistically significant (p less than 0.01). The exposed workers were subdivided according to presence or absence of radiological sign...

  8. Crystallization and preliminary crystallographic analysis of an octaketide-producing plant type III polyketide synthase.

    Science.gov (United States)

    Morita, Hiroyuki; Kondo, Shin; Kato, Ryohei; Wanibuchi, Kiyofumi; Noguchi, Hiroshi; Sugio, Shigetoshi; Abe, Ikuro; Kohno, Toshiyuki

    2007-11-01

    Octaketide synthase (OKS) from Aloe arborescens is a plant-specific type III polyketide synthase that produces SEK4 and SEK4b from eight molecules of malonyl-CoA. Recombinant OKS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group I422, with unit-cell parameters a = b = 110.2, c = 281.4 A, alpha = beta = gamma = 90.0 degrees . Diffraction data were collected to 2.6 A resolution using synchrotron radiation at BL24XU of SPring-8. PMID:18007047

  9. Connection between ambient density fluctuations and clumpy Langmuir waves in type III radio sources

    Science.gov (United States)

    Robinson, P. A.; Cairns, I. H.; Gurnett, D. A.

    1992-01-01

    A recent stochastic-growth theory of clumpy Langmuir waves in type III sources is shown to imply that the clumps will have the same size distribution as the ambient low-frequency density fluctuations in the solar wind. Spectral analysis of Langmuir-wave time series from the ISEE 3 plasma wave instrument confirms this prediction to within the uncertainties in the spectra. The smallest Langmuir clump size is inferred to be in the range 0.4-30 km in general, and 2-30 km for beam-resonant waves, and it is concluded that the diffusion of waves in the source is anomalous.

  10. Tyrosinemia type III: diagnosis and ten-year follow-up.

    Science.gov (United States)

    Cerone, R; Holme, E; Schiaffino, M C; Caruso, U; Maritano, L; Romano, C

    1997-09-01

    Tyrosinemia type III, caused by deficiency of 4-hydroxyphenylpyruvate dioxygenase, is a rare disorder of tyrosine catabolism. Primary 4-hydroxyphenylpyruvate dioxygenase deficiency has been described in only three patients. The biochemical phenotype shows hypertyrosinemia and elevated urinary excretion of 4-hydroxyphenyl derivatives. We report the clinical and biochemical findings and the results of long-term follow-up in a new patient with this disorder presenting with severe mental retardation and neurological abnormalities. The clinical phenotype is compared with those reported in the three previously described patients.

  11. H-alpha observations of the August 12, 1975 Type III-RS bursts

    Science.gov (United States)

    Labonte, B. J.

    1976-01-01

    We present H-alpha filtergram observations of a number of the Type III-RS (reverse slope) bursts that occurred on August 12, 1975. Solar radio emission was peculiar on that date in that a large number, and proportion, of the usually rare reverse slope bursts were observed (Tarnstrom and Zehntner, 1975). We show that the radio bursts coincide in time with a homologous set of H-alpha flares located at the limbward edge of spot group Mt. Wilson 19598. We propose a model in which the reverse slope bursts are the downward branches of U bursts, whose upward branches are hidden behind the coronal density enhancement over the spot group.

  12. Localization, by linkage analysis, of the cystinuria type III gene to chromosome 19q13.1

    Energy Technology Data Exchange (ETDEWEB)

    Bisceglia, L.; Totaro, A.; Melchionda, S. [and others

    1997-03-01

    Cystinuria is an autosomal recessive aminoaciduria in which three urinary phenotypes (I, II, and III) have been described. An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. Mutational and linkage analysis demonstrated the presence of genetic heterogeneity in which the SLC3A1 gene is responsible for type I cystinuria but not for type II or type III. In this study, we report the identification of the cystinuria type III locus on the long arm of chromosome 19 (19q13.1), obtained after a genomewide search. Pairwise linkage analysis in a series of type III or type II families previously excluded from linkage to the cystinuria type I locus (SLC3A1 gene) revealed a significant maximum LOD score (Z{sub max}) of 13.11 at a maximum recombination fraction ({theta}{sub max}) of .00, with marker D19S225. Multipoint linkage analysis performed with the use of additional markers from the region placed the cystinuria type III locus between D19S414 and D19S220. Preliminary data on type II families also seem to place the disease locus for this rare type of cystinuria at 19q13.1 (significant Z{sub max} = 3.11 at {theta}{sub max} of .00, with marker D19S225). 33 refs., 2 figs., 1 tab.

  13. Structure-function relationships within Keppler-type antitumor ruthenium(III) complexes: the case of 2-aminothiazolium[trans-tetrachlorobis(2-aminothiazole)ruthenate(III)].

    Science.gov (United States)

    Mura, Pasquale; Piccioli, Francesca; Gabbiani, Chiara; Camalli, Mercedes; Messori, Luigi

    2005-07-11

    Keppler-type ruthenium(III) complexes exhibit promising antitumor properties. We report here a study of 2-aminothiazolium[trans-tetrachlorobis(2-aminothiazole)ruthenate(III)], both in the solid state and in solution. The crystal structure has been solved and found to exhibit classical features. Important solvatochromic effects were revealed. Notably, we observed that introduction of an amino group in position 2 greatly accelerates chloride hydrolysis compared to the thiazole analogue; this latter finding may be of interest for a fine-tuning of the reactivity of these novel metallodrugs.

  14. Immunomodulation by the Pseudomonas syringae HopZ type III effector family in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Jennifer D Lewis

    Full Text Available Pseudomonas syringae employs a type III secretion system to inject 20-30 different type III effector (T3SE proteins into plant host cells. A major role of T3SEs is to suppress plant immune responses and promote bacterial infection. The YopJ/HopZ acetyltransferases are a superfamily of T3SEs found in both plant and animal pathogenic bacteria. In P. syringae, this superfamily includes the evolutionarily diverse HopZ1, HopZ2 and HopZ3 alleles. To investigate the roles of the HopZ family in immunomodulation, we generated dexamethasone-inducible T3SE transgenic lines of Arabidopsis for HopZ family members and characterized them for immune suppression phenotypes. We show that all of the HopZ family members can actively suppress various facets of Arabidopsis immunity in a catalytic residue-dependent manner. HopZ family members can differentially suppress the activation of mitogen-activated protein (MAP kinase cascades or the production of reactive oxygen species, whereas all members can promote the growth of non-virulent P. syringae. Localization studies show that four of the HopZ family members containing predicted myristoylation sites are localized to the vicinity of the plasma membrane while HopZ3 which lacks the myristoylation site is at least partially nuclear localized, suggesting diversification of immunosuppressive mechanisms. Overall, we demonstrate that despite significant evolutionary diversification, all HopZ family members can suppress immunity in Arabidopsis.

  15. Terminal reassortment drives the quantum evolution of type III effectors in bacterial pathogens.

    Directory of Open Access Journals (Sweden)

    John Stavrinides

    2006-10-01

    Full Text Available Many bacterial pathogens employ a type III secretion system to deliver type III secreted effectors (T3SEs into host cells, where they interact directly with host substrates to modulate defense pathways and promote disease. This interaction creates intense selective pressures on these secreted effectors, necessitating rapid evolution to overcome host surveillance systems and defenses. Using computational and evolutionary approaches, we have identified numerous mosaic and truncated T3SEs among animal and plant pathogens. We propose that these secreted virulence genes have evolved through a shuffling process we have called "terminal reassortment." In terminal reassortment, existing T3SE termini are mobilized within the genome, creating random genetic fusions that result in chimeric genes. Up to 32% of T3SE families in species with relatively large and well-characterized T3SE repertoires show evidence of terminal reassortment, as compared to only 7% of non-T3SE families. Terminal reassortment may permit the near instantaneous evolution of new T3SEs and appears responsible for major modifications to effector activity and function. Because this process plays a more significant role in the evolution of T3SEs than non-effectors, it provides insight into the evolutionary origins of T3SEs and may also help explain the rapid emergence of new infectious agents.

  16. Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.

    Science.gov (United States)

    Hashimoto, Shin; Yamamoto, Soh; Ogasawara, Noriko; Sato, Toyotaka; Yamamoto, Keisuke; Katoh, Hiroshi; Kubota, Toru; Shiraishi, Tsukasa; Kojima, Takashi; Himi, Tetsuo; Tsutsumi, Hiroyuki; Yokota, Shin-Ichi

    2016-01-01

    Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection. PMID:27560627

  17. Type III mixed cryoglobulinemia and antiphospholipid syndrome in a patient with partial DiGeorge syndrome.

    Science.gov (United States)

    Chang, Alice D; Tachdjian, Raffi; Gallagher, Kerry; McCurdy, Deborah K; Lassman, Charles; Stiehm, E Richard; Yadin, Ora

    2006-01-01

    We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated beta(2)-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

  18. Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome

    Directory of Open Access Journals (Sweden)

    Alice D. Chang

    2006-01-01

    Full Text Available We studied a 14 year-old boy with partial DiGeorge syndrome (DGS, status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT. Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF, and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF. This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection.

  19. Establishment of an inducing medium for type III effector secretion in Xanthomonas campestris pv. campestris

    Directory of Open Access Journals (Sweden)

    Guo-Feng Jiang

    2013-09-01

    Full Text Available It is well known that the type III secretion system (T3SS and type III (T3 effectors are essential for the pathogenicity of most bacterial phytopathogens and that the expression of T3SS and T3 effectors is suppressed in rich media but induced in minimal media and plants. To facilitate in-depth studies on T3SS and T3 effectors, it is crucial to establish a medium for T3 effector expression and secretion. Xanthomonas campestris pv. campestris (Xcc is a model bacterium for studying plant-pathogen interactions. To date no medium for Xcc T3 effector secretion has been defined. Here, we compared four minimal media (MME, MMX, XVM2, and XOM2 which are reported for T3 expression induction in Xanthomonas spp. and found that MME is most efficient for expression and secretion of Xcc T3 effectors. By optimization of carbon and nitrogen sources and pH value based on MME, we established XCM1 medium, which is about 3 times stronger than MME for Xcc T3 effectors secretion. We further optimized the concentration of phosphate, calcium, and magnesium in XCM1 and found that XCM1 with a lower concentration of magnesium (renamed as XCM2 is about 10 times as efficient as XCM1 (meanwhile, about 30 times stronger than MME. Thus, we established an inducing medium XCM2 which is preferred for T3 effector secretion in Xcc.

  20. Endofungal bacterium controls its host by an hrp type III secretion system.

    Science.gov (United States)

    Lackner, Gerald; Moebius, Nadine; Hertweck, Christian

    2011-02-01

    Burkholderia rhizoxinica and Rhizopus microsporus form a unique symbiosis in which intracellular bacteria produce the virulence factor of the phytopathogenic fungus. Notably, the host strictly requires endobacteria to sporulate. In this study, we show that the endofungal bacteria possess a type III secretion system (T3SS), which has a crucial role in the maintenance of the alliance. Mutants defective in type III secretion show reduced intracellular survival and fail to elicit sporulation of the host. Furthermore, genes coding for T3SS components are upregulated during cocultivation of the bacterial symbiont with their host. This is the first report on a T3SS involved in bacterial-fungal symbiosis. Phylogenetic analysis revealed that the T3SS represents a prototype of a clade of yet uncharacterized T3SSs within the hrp superfamily of T3SSs from plant pathogenic microorganisms. In a control experiment, we demonstrate that under laboratory conditions, rhizoxin production was not required for establishment of the symbiotic interaction. PMID:20720578

  1. LOFAR tied-array imaging of Type III solar radio bursts

    CERN Document Server

    Morosan, D E; Zucca, P; Fallows, R; Carley, E P; Mann, G; Bisi, M M; Kerdraon, A; Konovalenko, A A; MacKinnon, A L; Rucker, H O; Thidé, B; Magdalenić, J; Vocks, C; Reid, H; Anderson, J; Asgekar, A; Avruch, I M; Bentum, M J; Bernardi, G; Best, P; Bonafede, A; Bregman, J; Breitling, F; Broderick, J; Brüggen, M; Butcher, H R; Ciardi, B; Conway, J E; de Gasperin, F; de Geus, E; Deller, A; Duscha, S; Eislöffel, J; Engels, D; Falcke, H; Ferrari, C; Frieswijk, W; Garrett, M A; Grießmeier, J; Gunst, A W; Hassall, T E; Hessels, J W T; Hoeft, M; Hörandel, J; Horneffer, A; Iacobelli, M; Juette, E; Karastergiou, A; Kondratiev, V I; Kramer, M; Kuniyoshi, M; Kuper, G; Maat, P; Markoff, S; McKean, J P; Mulcahy, D D; Munk, H; Nelles, A; Norden, M J; Orru, E; Paas, H; Pandey-Pommier, M; Pandey, V N; Pietka, G; Pizzo, R; Polatidis, A G; Reich, W; Röttgering, H; Scaife, A M M; Schwarz, D; Serylak, M; Smirnov, O; Stappers, B W; Stewart, A; Tagger, M; Tang, Y; Tasse, C; Thoudam, S; Toribio, C; Vermeulen, R; van Weeren, R J; Wucknitz, O; Yatawatta, S; Zarka, P

    2014-01-01

    The Sun is an active source of radio emission which is often associated with energetic phenomena such as solar flares and coronal mass ejections (CMEs). At low radio frequencies (<100 MHz), the Sun has not been imaged extensively because of the instrumental limitations of previous radio telescopes. Here, the combined high spatial, spectral and temporal resolution of the Low Frequency Array (LOFAR) was used to study solar Type III radio bursts at 30-90 MHz and their association with CMEs. The Sun was imaged with 126 simultaneous tied-array beams within 5 solar radii of the solar centre. This method offers benefits over standard interferometric imaging since each beam produces high temporal (83 ms) and spectral resolution (12.5 kHz) dynamic spectra at an array of spatial locations centred on the Sun. LOFAR's standard interferometric output is currently limited to one image per second. Over a period of 30 minutes, multiple Type III radio bursts were observed, a number of which were found to be located at high...

  2. Pore-forming Activity of the Escherichia coli Type III Secretion System Protein EspD.

    Science.gov (United States)

    Chatterjee, Abhishek; Caballero-Franco, Celia; Bakker, Dannika; Totten, Stephanie; Jardim, Armando

    2015-10-16

    Enterohemorrhagic Escherichia coli is a causative agent of gastrointestinal and diarrheal diseases. Pathogenesis associated with enterohemorrhagic E. coli involves direct delivery of virulence factors from the bacteria into epithelial cell cytosol via a syringe-like organelle known as the type III secretion system. The type III secretion system protein EspD is a critical factor required for formation of a translocation pore on the host cell membrane. Here, we show that recombinant EspD spontaneously integrates into large unilamellar vesicle (LUV) lipid bilayers; however, pore formation required incorporation of anionic phospholipids such as phosphatidylserine and an acidic pH. Leakage assays performed with fluorescent dextrans confirmed that EspD formed a structure with an inner diameter of ∼2.5 nm. Protease mapping indicated that the two transmembrane helical hairpin of EspD penetrated the lipid layer positioning the N- and C-terminal domains on the extralumenal surface of LUVs. Finally, a combination of glutaraldehyde cross-linking and rate zonal centrifugation suggested that EspD in LUV membranes forms an ∼280-320-kDa oligomeric structure consisting of ∼6-7 subunits.

  3. Adenocarcinoma arising in a heterotopic pancreas (Heinrich type III: a case report

    Directory of Open Access Journals (Sweden)

    Egashira Yutaro

    2010-02-01

    Full Text Available Abstract Introduction Heterotopic pancreatic cancer in the duodenum is a very rare disease. Only twelve cases have been reported worldwide to date. We report a rare case of malignant transformation of heterotopic pancreas (Heinrich type III in the duodenum with long-term survival of the patient, and review the 12 cases in the literature. Case presentation A 75-year-old Japanese man was admitted to our hospital complaining of nausea and vomiting. Endoscopy and upper gastrointestinal contrast study showed marked duodenal stenosis. A pylorus-preserving pancreaticoduodenectomy was performed. Histopathological examination of the surgically resected specimen showed malignant transformation of heterotopic pancreas (Heinrich type III in the duodenum. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 30. He is well and shows no signs of recurrence at the time of writing, six years after the surgery. Conclusion Adenocarcinoma arising within the heterotopic pancreas appears to be rare. It is difficult to obtain a correct diagnosis preoperatively. The management of heterotopic pancreas depends on the presence or absence of symptoms. If the patient is asymptomatic or benign, conservative treatment with regular follow-up is recommended. When the patient is symptomatic or there is a suspicion of malignancy, surgical management with intra-operative frozen section diagnosis is indicated.

  4. High frequency ion sound waves associated with Langmuir waves in type III radio burst source regions

    Directory of Open Access Journals (Sweden)

    G. Thejappa

    2004-01-01

    Full Text Available Short wavelength ion sound waves (2-4kHz are detected in association with the Langmuir waves (~15-30kHz in the source regions of several local type III radio bursts. They are most probably not due to any resonant wave-wave interactions such as the electrostatic decay instability because their wavelengths are much shorter than those of Langmuir waves. The Langmuir waves occur as coherent field structures with peak intensities exceeding the Langmuir collapse thresholds. Their scale sizes are of the order of the wavelength of an ion sound wave. These Langmuir wave field characteristics indicate that the observed short wavelength ion sound waves are most probably generated during the thermalization of the burnt-out cavitons left behind by the Langmuir collapse. Moreover, the peak intensities of the observed short wavelength ion sound waves are comparable to the expected intensities of those ion sound waves radiated by the burnt-out cavitons. However, the speeds of the electron beams derived from the frequency drift of type III radio bursts are too slow to satisfy the needed adiabatic ion approximation. Therefore, some non-linear process such as the induced scattering on thermal ions most probably pumps the beam excited Langmuir waves towards the lower wavenumbers, where the adiabatic ion approximation is justified.

  5. Percutaneous K-wiring for Gartland type III supracondylar humerus fractures in children

    International Nuclear Information System (INIS)

    To assess the ability of closed reduction and percutanepous K-wire fixation, to obtain and maintain an adequate reduction, and thereby achieve satisfactory end results. A prospective study conducted on 60 children over 28 months at Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India, from March 2003 to June 2005, in which Gartland type-III supracondylar fracture humerus were treated by closed reduction and percutaneous pinning either from lateral side only from medical side also, under image intensifier control. There was no problem in union. Patients were graded by Flynn's criteria with excellent results in 88.88%, good in 4.44% cases. Only one patient had developed cubitus varus deformity and one had Iatrogenic Ulnar nerve palsy from medial pin, which recovered subsequently. The Baumann's angle was well with in the normal range of 66-840. Percutaneous K-wire fixation is a safe and effective method for the management of Gartland type III Supracondylar fractures with minimal hospital stay and without risking vascular compromise. (author)

  6. Tenascin C promiscuously binds growth factors via its fifth fibronectin type III-like domain.

    Directory of Open Access Journals (Sweden)

    Laura De Laporte

    Full Text Available Tenascin C (TNC is an extracellular matrix protein that is upregulated during development as well as tissue remodeling. TNC is comprised of multiple independent folding domains, including 15 fibronectin type III-like (TNCIII domains. The fifth TNCIII domain (TNCIII5 has previously been shown to bind heparin. Our group has shown that the heparin-binding fibronectin type III domains of fibronectin (FNIII, specifically FNIII12-14, possess affinity towards a large number of growth factors. Here, we show that TNCIII5 binds growth factors promiscuously and with high affinity. We produced recombinant fragments of TNC representing the first five TNCIII repeats (TNCIII1-5, as well as subdomains, including TNCIII5, to study interactions with various growth factors. Multiple growth factors of the platelet-derived growth factor (PDGF family, the fibroblast growth factor (FGF family, the transforming growth factor beta (TGF-β superfamily, the insulin-like growth factor binding proteins (IGF-BPs, and neurotrophins were found to bind with high affinity to this region of TNC, specifically to TNCIII5. Surface plasmon resonance was performed to analyze the kinetics of binding of TNCIII1-5 with TGF-β1, PDGF-BB, NT-3, and FGF-2. The promiscuous yet high affinity of TNC for a wide array of growth factors, mediated mainly by TNCIII5, may play a role in multiple physiological and pathological processes involving TNC.

  7. Collagen Type III and VI Turnover in Response to Long-Term Immobilization

    DEFF Research Database (Denmark)

    Sun, Shu; Henriksen, Kim; Karsdal, Morten A;

    2015-01-01

    biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated......BACKGROUND: Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide...... with immobilization and/or remobilization. METHODS: In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured...

  8. Increased Levels of Type I and III Collagen and Hyaluronan in Scleroderma Skin

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Heickendorff, Lene; L, Risteli;

    1997-01-01

    The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were...... from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin of patients. The median value of suction blister PIIINP from the transition zone was 38% higher than suction blister PIIINP from uninvolved skin. PIIINP was localized to the dermis by immunohistochemical...... techniques. PICP and HA levels in blisters from the transition zone were 87% and 53%, respectively, above the levels measured in uninvolved skin. Furthermore, PICP and HA blister levels from the transition zone were 67% and 63%, respectively, higher than the levels measured in healthy volunteers. In plasma...

  9. Subtypes of batterers in treatment: empirical support for a distinction between type I, type II and type III.

    Science.gov (United States)

    Graña, José Luis; Redondo, Natalia; Muñoz-Rivas, Marina J; Cantos, Arthur L

    2014-01-01

    This study explores the existence of different types of batterers in a sample of 266 men who had been court referred for intimate partner violence. The data collected in the assessment that have been used to perform a hierarchical and a two-step cluster analysis fall into three areas: aggression towards the partner, general aggression and presence of psychopathology and personality traits, more specifically, alcohol use, borderline and antisocial personality traits, psychopathy traits, state anger and trait anger, anger expression and control, anger, hostility, and, finally, impulsivity. The results show a typology consisting of 3 types of batterers on the basis of violence level and psychopathology: low (65%), moderate (27.8%) and high (7.1%). This study provides empirical support for the development of batterer typologies. These typologies will help achieve early detection of different types of batterers, allowing us to tailor interventions on the basis of the needs of each of the types. PMID:25329828

  10. Subtypes of batterers in treatment: empirical support for a distinction between type I, type II and type III.

    Directory of Open Access Journals (Sweden)

    José Luis Graña

    Full Text Available This study explores the existence of different types of batterers in a sample of 266 men who had been court referred for intimate partner violence. The data collected in the assessment that have been used to perform a hierarchical and a two-step cluster analysis fall into three areas: aggression towards the partner, general aggression and presence of psychopathology and personality traits, more specifically, alcohol use, borderline and antisocial personality traits, psychopathy traits, state anger and trait anger, anger expression and control, anger, hostility, and, finally, impulsivity. The results show a typology consisting of 3 types of batterers on the basis of violence level and psychopathology: low (65%, moderate (27.8% and high (7.1%. This study provides empirical support for the development of batterer typologies. These typologies will help achieve early detection of different types of batterers, allowing us to tailor interventions on the basis of the needs of each of the types.

  11. Nitrated type III collagen as a biological marker of nitric oxide-mediated synovial tissue metabolism in osteoarthritis

    DEFF Research Database (Denmark)

    Richardot, P; Charni-Ben Tabassi, N; Toh, L;

    2009-01-01

    OBJECTIVES: Nitric oxide (NO) is a major mediator of joint tissue inflammation and damage in osteoarthritis (OA) and mediates the nitration of tyrosine (Y*) residues in proteins. We investigated the nitration of type III collagen, a major constituent of synovial membrane, in knee OA. METHODS: A...... polyclonal antibody directed against the nitrated QY*DSY*DVKSG sequence from type III collagen N-telopeptide was generated. Synovial tissues from patients with knee OA (n=4) and rheumatoid arthritis (RA, n=4) were analyzed by immunohistochemistry for IIINys. Serum IIINys levels were measured by enzyme......-linked immunosorbent assay in 87 patients with painful knee OA (mean age: 63.0+/-8.0 years, Kellgren-Lawrence score II-III) and in 40 sex and age-matched healthy controls. RESULTS: Competition experiments using various nitrated and un-nitrated type III collagen and derived sequences, showed that the antibody was...

  12. Type- and Subcomplex-Specific Neutralizing Antibodies against Domain III of Dengue Virus Type 2 Envelope Protein Recognize Adjacent Epitopes▿

    Science.gov (United States)

    Sukupolvi-Petty, Soila; Austin, S. Kyle; Purtha, Whitney E.; Oliphant, Theodore; Nybakken, Grant E.; Schlesinger, Jacob J.; Roehrig, John T.; Gromowski, Gregory D.; Barrett, Alan D.; Fremont, Daved H.; Diamond, Michael S.

    2007-01-01

    Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials. PMID:17881453

  13. Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes.

    Science.gov (United States)

    Sukupolvi-Petty, Soila; Austin, S Kyle; Purtha, Whitney E; Oliphant, Theodore; Nybakken, Grant E; Schlesinger, Jacob J; Roehrig, John T; Gromowski, Gregory D; Barrett, Alan D; Fremont, Daved H; Diamond, Michael S

    2007-12-01

    Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials.

  14. Spectroscopic Identification of Type 2 Quasars at Z < 1 in SDSS-III/BOSS

    CERN Document Server

    Yuan, Sihan; Zakamska, Nadia L

    2016-01-01

    The physics and demographics of type 2 quasars remain poorly understood, and new samples of such objects selected in a variety of ways can give insight into their physical properties, evolution, and relationship to their host galaxies. We present a sample of 2758 type 2 quasars at z $\\leq$ 1 from the SDSS-III/BOSS spectroscopic database, selected on the basis of their emission-line properties. We probe the luminous end of the population by requiring the rest-frame equivalent width of [OIII] to be > 100 {\\AA}. We distinguish our objects from star-forming galaxies and type 1 quasars using line widths, standard emission line ratio diagnostic diagrams at z 0.52. The majority of our objects have [OIII] luminosities in the range 10^8.5-10^10 L$_{\\odot}$ and redshifts between 0.4 and 0.65. Our sample includes over 400 type 2 quasars with incorrectly measured redshifts in the BOSS database; such objects often show kinematic substructure or outflows in the [OIII] line. The majority of the sample has counterparts in t...

  15. Changes in histoanatomical distribution of types I, III and V collagen promote adaptative remodeling in posterior tibial tendon rupture

    Directory of Open Access Journals (Sweden)

    Érika Satomi

    2008-01-01

    Full Text Available INTRODUCTION: Posterior tibial tendon dysfunction is a common cause of adult flat foot deformity, and its etiology is unknown. PURPOSE: In this study, we characterized the morphologic pattern and distribution of types I, III and V collagen in posterior tibial tendon dysfunction. METHOD: Tendon samples from patients with and without posterior tibial tendon dysfunction were stained by immunofluorescence using antibodies against types I, III and V collagen. RESULTS: Control samples showed that type V deposited near the vessels only, while surgically obtained specimens displayed type V collagen surrounding other types of collagen fibers in thicker adventitial layers. Type III collagen levels were also increased in pathological specimens. On the other hand, amounts of collagen type I, which represents 95% of the total collagen amount in normal tendon, were decreased in pathological specimens. CONCLUSION: Fibrillogenesis in posterior tibial tendon dysfunction is altered due to higher expression of types III and V collagen and a decreased amount of collagen type I, which renders the originating fibrils structurally less resistant to mechanical forces.

  16. Subtypes of Batterers in Treatment: Empirical Support for a Distinction between Type I, Type II and Type III

    OpenAIRE

    José Luis Graña; Natalia Redondo; Muñoz-Rivas, Marina J.; Arthur L Cantos

    2014-01-01

    This study explores the existence of different types of batterers in a sample of 266 men who had been court referred for intimate partner violence. The data collected in the assessment that have been used to perform a hierarchical and a two-step cluster analysis fall into three areas: aggression towards the partner, general aggression and presence of psychopathology and personality traits, more specifically, alcohol use, borderline and antisocial personality traits, psychopathy traits, state ...

  17. Type I, II, and III Interferons: Regulating Immunity to Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Travar, Maja; Petkovic, Miroslav; Verhaz, Antonija

    2016-02-01

    Interferons (IFNs) are cytokines released by host cells in response to the presence of pathogens or tumor cells. The aim of this review was to present the previously known and new findings about the role of interferons type I and II, and recently discovered type III in Mycobacterium tuberculosis (M. tuberculosis) infection control. Infection of various cell types with M. tuberculosis induce both IFN-α and IFN-β synthesis. The majority of the studies support the findings that IFN type I actually promotes infection with M. tuberculosis. It has been well establish that IFN-γ has protective function against M. tuberculosis and the other mycobacteria and that the primary source of this cytokine are CD4(+) and CD8(+) T cells. Recently, it has been shown that also the innate lymphocytes, γδ T cells, natural killer (NK) T cells, and NK cells can also be the source of IFN-γ in response to mycobacterial infection. Several studies have shown that CD4(+) T cells protect mice against M. tuberculosis independently of IFN-γ. The balance between IFN-γ and different cytokines such as IL-10 and other Th2 cell cytokines is likely to influence disease outcome. Type I IFN appears to be detrimental through at least three separate, but overlapping, type I IFN-mediated mechanisms: induction of excessive apoptosis, specific suppression of Th1 and IFN-γ responses, and dampening of the immune response by strong IL-10 induction. Recently it has been found that M. tuberculosis infection in A549 lung epithelial cells stimulate up-regulation of IFN-λ genes in vitro. IFN-λs also have a role in modulation of Th1/Th2 response. IFN-λs are not essential for M. tuberculosis infection control, but can give some contribution in immune response to this pathogen.

  18. Non-LTE calculations of Al III line strengths in early-type stars

    Energy Technology Data Exchange (ETDEWEB)

    Dufton, P.L.; Brown, P.J.F.; Lennon, D.J.; Lynas-Gray, A.E.

    1986-10-15

    Non-LTE line formation calculations, based on the 'complete linearization method' are presented for the Al III ion in early-type stars. Equivalent widths, together with the corresponding LTE values, are tabulated for 15 ultraviolet and visible region transitions, for effective temperatures from 20 000 to 35 000 K, logarithmic gravities of 3.5, 4.0 and 4.5, microturbulent velocities of 0 and 5 km s/sup -1/ and logarithmic aluminium abundances of 6.0, 6.5 and 7.0. The non-LTE line strengths are significantly larger than the LTE values particularly for the visible region transitions and the implications of this are briefly discussed.

  19. Non-LTE calculations of Al III line strengths in early-type stars

    International Nuclear Information System (INIS)

    Non-LTE line formation calculations, based on the 'complete linearization method' are presented for the Al III ion in early-type stars. Equivalent widths, together with the corresponding LTE values, are tabulated for 15 ultraviolet and visible region transitions, for effective temperatures from 20 000 to 35 000 K, logarithmic gravities of 3.5, 4.0 and 4.5, microturbulent velocities of 0 and 5 km s-1 and logarithmic aluminium abundances of 6.0, 6.5 and 7.0. The non-LTE line strengths are significantly larger than the LTE values particularly for the visible region transitions and the implications of this are briefly discussed. (author)

  20. Relationship of Type III Radio Bursts with Quasi-periodic Pulsations in a Solar Flare

    Science.gov (United States)

    Kupriyanova, E. G.; Kashapova, L. K.; Reid, H. A. S.; Myagkova, I. N.

    2016-08-01

    We studied a solar flare with pronounced quasi-periodic pulsations detected in the microwave, X-ray, and radio bands. We used correlation, Fourier, and wavelet analyses methods to examine the temporal fine structures and relationships between the time profiles in each wave band. We found that the time profiles of the microwaves, hard X-rays, and type III radio bursts vary quasi-periodically with a common period of 40 - 50 s. The average amplitude of the variations is high, above 30 % of the background flux level, and reaches 80 % after the flare maximum. We did not find this periodicity in either the thermal X-ray flux component or in the source size dynamics. Our findings indicate that the detected periodicity is probably associated with periodic dynamics in the injection of non-thermal electrons, which can be produced by periodic modulation of magnetic reconnection.

  1. Relationship of type III radio bursts with quasi-periodic pulsations in a solar flare

    CERN Document Server

    Kupriyanova, E G; Reid, H A S; Myagkova, I N

    2016-01-01

    We studied a solar flare with pronounced quasi-periodic pulsations detected in the microwave, X-ray, and radio bands. We used the methods of correlation, Fourier, and wavelet analyses to examine the temporal fine structures and relationships between the time profiles in each wave band. We found that the time profiles of the microwaves, hard X-rays and type III radio bursts vary quasi-periodically with the common period of 40-50 s. The average amplitude of the variations is high, above 30% of the background flux level and reaching 80% after the flare maximum. We did not find the periodicity in either the thermal X-ray flux component or source size dynamics. Our findings indicate that the detected periodicity is likely to be associated with periodic dynamics in the injection of non-thermal electrons, that can be produced by periodic modulation of magnetic reconnection.

  2. Pseudomonas syringae type III effector repertoires: last words in endless arguments.

    Science.gov (United States)

    Lindeberg, Magdalen; Cunnac, Sébastien; Collmer, Alan

    2012-04-01

    Many plant pathogens subvert host immunity by injecting compositionally diverse but functionally similar repertoires of cytoplasmic effector proteins. The bacterial pathogen Pseudomonas syringae is a model for exploring the functional structure of such repertoires. The pangenome of P. syringae encodes 57 families of effectors injected by the type III secretion system. Distribution of effector genes among phylogenetically diverse strains reveals a small set of core effectors targeting antimicrobial vesicle trafficking and a much larger set of variable effectors targeting kinase-based recognition processes. Complete disassembly of the 28-effector repertoire of a model strain and reassembly of a minimal functional repertoire reveals the importance of simultaneously attacking both processes. These observations, coupled with growing knowledge of effector targets in plants, support a model for coevolving molecular dialogs between effector repertoires and plant immune systems that emphasizes mutually-driven expansion of the components governing recognition. PMID:22341410

  3. Plant targets for Pseudomonas syringae type III effectors: virulence targets or guarded decoys?

    Science.gov (United States)

    Block, Anna; Alfano, James R

    2011-02-01

    The phytopathogenic bacterium Pseudomonas syringae can suppress both pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) by the injection of type III effector (T3E) proteins into host cells. T3Es achieve immune suppression using a variety of strategies including interference with immune receptor signaling, blocking RNA pathways and vesicle trafficking, and altering organelle function. T3Es can be recognized indirectly by resistance proteins monitoring specific T3E targets resulting in ETI. It is presently unclear whether the monitored targets represent bona fide virulence targets or guarded decoys. Extensive overlap between PTI and ETI signaling suggests that T3Es may suppress both pathways through common targets and by possessing multiple activities. PMID:21227738

  4. The Pseudomonas aeruginosa Type III Translocon Is Required for Biofilm Formation at the Epithelial Barrier

    DEFF Research Database (Denmark)

    Tran, Cindy S; Rangel, Stephanie M; Almblad, Henrik;

    2014-01-01

    Clinical infections by Pseudomonas aeruginosa, a deadly Gram-negative, opportunistic pathogen of immunocompromised hosts, often involve the formation of antibiotic-resistant biofilms. Although biofilm formation has been extensively studied in vitro on glass or plastic surfaces, much less is known...... about biofilm formation at the epithelial barrier. We have previously shown that when added to the apical surface of polarized epithelial cells, P. aeruginosa rapidly forms cell-associated aggregates within 60 minutes of infection. By confocal microscopy we now show that cell-associated aggregates...... a previously unappreciated function for the type III translocon in the formation of P. aeruginosa biofilms at the epithelial barrier and demonstrate that biofilms may form at early time points of infection....

  5. Successful stabilisation of a type III paediatric tibial eminence fracture using a tensioned wire technique.

    Science.gov (United States)

    Archer, Matthew; Parkin, Tom; Latimer, Mark David

    2016-01-01

    We report the case of an 11-year-old boy presenting with a type III tibial eminence fracture. The fracture fragment was reduced arthroscopically. Two 1.6 mm retrograde K-wires were inserted from the tibial metaphysis across the physis and into the fracture fragment using a standard anterior cruciate ligament tibial tunnel guide. Once the wires were clearly visible within the joint the tips were bent over by ∼120°. The wires were then tensioned around a single small fragment screw inserted into the tibial metaphysis. An exceptionally strong fixation was achieved. The boy was mobilised without a brace. The wires were removed at 12 weeks and he returned to full activity at 14 weeks. PMID:27646317

  6. The SPI-1-like Type III secretion system: more roles than you think.

    Science.gov (United States)

    Egan, Frank; Barret, Matthieu; O'Gara, Fergal

    2014-01-01

    The type III secretion system (T3SS) is a protein delivery system which is involved in a wide spectrum of interactions, from mutualism to pathogenesis, between Gram negative bacteria and various eukaryotes, including plants, fungi, protozoa and mammals. Various phylogenetic families of the T3SS have been described, including the Salmonella Pathogenicity Island 1 family (SPI-1). The SPI-1 T3SS was initially associated with the virulence of enteric pathogens, but is actually found in a diverse array of bacterial species, where it can play roles in processes as different as symbiotic interactions with insects and colonization of plants. We review the multiple roles of the SPI-1 T3SS and discuss both how these discoveries are changing our perception of the SPI-1 family and what impacts this has on our understanding of the specialization of the T3SS in general.

  7. Crystallization and preliminary crystallographic analysis of an octaketide-producing plant type III polyketide synthase

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Hiroyuki [Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511 (Japan); Kondo, Shin; Kato, Ryohei [Innovation Center Yokohama, Mitsubishi Chemical Corporation, 1000 Kamoshida, Aoba, Yokohama, Kanagawa 227-8502 (Japan); Wanibuchi, Kiyofumi; Noguchi, Hiroshi [School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526 (Japan); Sugio, Shigetoshi, E-mail: sugio.shigetoshi@mw.m-kagaku.co.jp [Innovation Center Yokohama, Mitsubishi Chemical Corporation, 1000 Kamoshida, Aoba, Yokohama, Kanagawa 227-8502 (Japan); Abe, Ikuro, E-mail: sugio.shigetoshi@mw.m-kagaku.co.jp [School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526 (Japan); PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kohno, Toshiyuki, E-mail: sugio.shigetoshi@mw.m-kagaku.co.jp [Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511 (Japan)

    2007-11-01

    Octaketide synthase from A. arborescens has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 2.6 Å. Octaketide synthase (OKS) from Aloe arborescens is a plant-specific type III polyketide synthase that produces SEK4 and SEK4b from eight molecules of malonyl-CoA. Recombinant OKS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group I422, with unit-cell parameters a = b = 110.2, c = 281.4 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.6 Å resolution using synchrotron radiation at BL24XU of SPring-8.

  8. Crystallization and preliminary crystallographic analysis of an octaketide-producing plant type III polyketide synthase

    International Nuclear Information System (INIS)

    Octaketide synthase from A. arborescens has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 2.6 Å. Octaketide synthase (OKS) from Aloe arborescens is a plant-specific type III polyketide synthase that produces SEK4 and SEK4b from eight molecules of malonyl-CoA. Recombinant OKS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group I422, with unit-cell parameters a = b = 110.2, c = 281.4 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.6 Å resolution using synchrotron radiation at BL24XU of SPring-8

  9. Crystallization and preliminary crystallographic analysis of a plant type III polyketide synthase that produces benzalacetone

    International Nuclear Information System (INIS)

    Benzalacetone synthase from R. palmatum has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to a resolution of 1.8 Å. Benzalacetone synthase (BAS) from Rheum palmatum is a plant-specific type III polyketide synthase that catalyzes the one-step decarboxylative condensation of 4-coumaroyl-CoA with malonyl-CoA to produce the diketide 4-(4-hydroxyphenyl)-but-3-en-2-one. Recombinant BAS expressed in Escherichia coli was crystallized by the sitting-drop vapour-diffusion method. The crystals belong to space group P21, with unit-cell parameters a = 54.6, b = 89.6, c = 81.1 Å, α = γ = 90.0, β = 100.5°. Diffraction data were collected to 1.8 Å resolution using synchrotron radiation at BL24XU of SPring-8

  10. A clinical report of Type III dens invaginatus: relevant aspects of a combined therapeutic approach.

    Science.gov (United States)

    Silva E Souza, Patricia de Almeida Rodrigues; de Almeida, Bruno Vila Nova; Tartari, Talita; Alves, Ana Claudia Braga Amoras; Tuji, Farbicio Mesquita; Silva E Souza, Mario Honorato

    2013-01-01

    Dens invaginatus is a developmental abnormality that alters dental morphology; as a result, treating this condition is a challenge for endodontic practices. This article describes how a combination of nonsurgical and surgical therapies was utilized to treat a maxillary central incisor with Type III dens invaginatus and vital pulp. The treatment plan included using computed tomography (CT) for a detailed analysis of the dental anatomy and periapical area, endodontic and surgical procedures, and a 4-year follow-up period that included periodic clinical and radiographic examinations. The follow-up examinations revealed a regression of the apical lesion and no other signs or symptoms. Based on the present case report, the authors concluded that this combination of surgical and nonsurgical approaches was effective and that CT is a valuable auxiliary tool for the study of dental anatomy.

  11. Decays $h\\to \\gamma \\gamma, \\, \\gamma Z$ in the Two Higgs Doublet Model Type III

    CERN Document Server

    Cordero-Cid, A; Honorato, C G; Moretti, S

    2015-01-01

    We study the enhancement of the branching ratios of the decays $h \\to \\gamma \\gamma, \\, \\gamma Z$ in the Two Higgs Doublet Model Type III, assuming a four-zero Yukawa Texture and a general Higgs potential. We show that these processes are very sensitive to the flavor pattern of the Yukawa texture and the structure of the triple coupling $h H^\\pm H^\\mp$ from the Higgs potential. We can accomodate the parameters of the model such that one can obtain the $h \\to\\gamma \\gamma$ rates reported by the LHC and at the same time we can get a $ h \\to \\gamma Z$ fraction larger than in the SM and within experimental reach. The possibility of obtaining a light charged Higgs boson within the ensuing parameter space and compatible with current experimental measurements is also presented.

  12. Chemical shift assignments of the fibronectin III like domains 7-8 of type VII collagen.

    Science.gov (United States)

    Hermsdorf, Ulrike; Seeger, Karsten

    2016-04-01

    Type VII collagen (Col7) is important for skin stability. This is underlined by the severe skin blistering phenotype in the Col7 related diseases dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita (EBA). Col7 has a large N-terminal non-collagenous domain (NC1) that is followed by the triple helical collagenous domain. The NC1 domain has subdomains with homology to adhesion molecules and mediates important interactions within the extracellular matrix. An 185 amino acid long part of the NC1-subdomain termed fibronectin III like domains 7 and 8 (FNIII7-8) was investigated. Antibodies against this region are pathogenic in a mouse model of EBA and one reported missense mutations of Col7 lies within these domains. The nearly complete NMR resonance assignment of recombinant FNIII7-8 of Col7 is reported. PMID:26364055

  13. Lepton Flavor Violation in the Two Higgs Doublet Model type III

    CERN Document Server

    Díaz, R; Rodríguez, José Alberto

    2001-01-01

    We consider a two Higgs doublet model type III which produces Flavour Changing Neutral Currents (FCNC) at tree level in the leptonic sector. In the framework of this model we have two situations: when both doublets acquire a vacuum expectation value different from zero and the case when only one of them get it. We find that both models contain the Standard Model in the decoupling limit for the Higgs fields but in the former FCNC at tree level remains by means of the interaction with the would-be Goldstone boson of Z, meanwhile in the latter these ones are completely absent. We get an upper bound for the flavour changing factor $N_{\\mu e}$ in the decoupling limit using the rare processes $\\mu \\to e \\gamma$ and $\\mu \\to eee$. Also, we present allowed regions in the $N_{\\mu e}-m_{h^0}$ plane.

  14. Effect of using heat-inactivated serum with the Abbott human T-cell lymphotropic virus type III antibody test.

    OpenAIRE

    Jungkind, D. L.; DiRenzo, S A; Young, S J

    1986-01-01

    The Abbott enzyme immunoassay (Abbott Laboratories, North Chicago, Ill.) for human T-cell lymphotropic virus type III (HTLV-III) antibody was evaluated to determine the effect of using heat-inactivated (56 degrees C for 30 min) serum as the sample. Each of 58 nonreactive serum samples gave a higher A492 value when tested after heat inactivation. Ten of the samples became reactive after heating. Heat-inactivated serum should not be used in the current Abbott HTLV-III antibody test, because thi...

  15. Cross-complementation study of the flagellar type III export apparatus membrane protein FlhB.

    Directory of Open Access Journals (Sweden)

    Clive S Barker

    Full Text Available The bacterial type III export apparatus is found in the flagellum and in the needle complex of some pathogenic Gram-negative bacteria. In the needle complex its function is to secrete effector proteins for infection into Eukaryotic cells. In the bacterial flagellum it exports specific proteins for the building of the flagellum during its assembly. The export apparatus is composed of about five membrane proteins and three soluble proteins. The mechanism of the export apparatus is not fully understood. The five membrane proteins are well conserved and essential. Here a cross-complementation assay was performed: substituting in the flagellar system of Salmonella one of these membrane proteins, FlhB, by the FlhB ortholog from Aquifex aeolicus (an evolutionary distant hyperthermophilic bacteria or a chimeric protein (AquSalFlhB made by the combination of the trans-membrane domain of A. aeolicus FlhB with the cytoplasmic domain of Salmonella FlhB dramatically reduced numbers of flagella and motility. From cells expressing the chimeric AquSalFlhB protein, suppressor mutants with enhanced motility were isolated and the mutations were identified using whole genome sequencing. Gain-of-function mutations were found in the gene encoding FlhA, another membrane protein of the type III export apparatus. Also, mutations were identified in genes encoding 4-hydroxybenzoate octaprenyltransferase, ubiquinone/menaquinone biosynthesis methyltransferase, and 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, which are required for ubiquinone biosynthesis. The mutations were shown by reversed-phase high performance liquid chromatography to reduce the quinone pool of the cytoplasmic membrane. Ubiquinone biosynthesis could be restored for the strain bearing a mutated gene for 4-hydroxybenzoate octaprenyltransferase by the addition of excess exogenous 4-hydroxybenzoate. Restoring the level of ubiquinone reduced flagella biogenesis with the AquSalFlhB chimera

  16. Global impact of Salmonella type III secretion effector SteA on host cells

    Energy Technology Data Exchange (ETDEWEB)

    Cardenal-Muñoz, Elena, E-mail: e_cardenal@us.es; Gutiérrez, Gabriel, E-mail: ggpozo@us.es; Ramos-Morales, Francisco, E-mail: framos@us.es

    2014-07-11

    Highlights: • We analyzed HeLa cells transcriptome in response to Salmonella SteA. • Significant differential expression was detected for 58 human genes. • They are involved in ECM organization and regulation of some signaling pathways. • Cell death, cell adhesion and cell migration were decreased in SteA-expressing cells. • These results contribute to understand the role of SteA during infections. - Abstract: Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems, encoded in pathogenicity islands 1 and 2. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both type III secretion systems. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also causes repression of genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. In addition, a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, and decreased cytotoxicity, cell–cell adhesion and migration.

  17. A DECADE OF SOLAR TYPE III RADIO BURSTS OBSERVED BY THE NANCAY RADIOHELIOGRAPH 1998-2008

    Energy Technology Data Exchange (ETDEWEB)

    Saint-Hilaire, P. [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Vilmer, N.; Kerdraon, A., E-mail: shilaire@ssl.berkeley.edu [LESIA, Observatoire de Paris, CNRS, UPMC, Universite Paris-Diderot 5 place Jules Janssen, F-92195 Meudon (France)

    2013-01-01

    We present a statistical survey of almost 10,000 radio type III bursts observed by the Nancay Radioheliograph from 1998 to 2008, covering nearly a full solar cycle. In particular, sources sizes, positions, and fluxes were examined. We find an east-west asymmetry in source positions that could be attributed to a 6 Degree-Sign {+-} 1 Degree-Sign eastward tilt of the magnetic field, that source FWHM sizes s roughly follow a solar-cycle-averaged distribution (dN/ds) Almost-Equal-To 14 {nu}{sup -3.3} s {sup -4} arcmin{sup -1} day{sup -1}, and that source fluxes closely follow a solar-cycle-averaged (dN/ds {sub {nu}}) Almost-Equal-To 0.34 {nu}{sup -2.9} S {sup -1.7} {sub {nu}} sfu{sup -1} day{sup -1} distribution (when {nu} is in GHz, s in arcminutes, and S {sub {nu}} in sfu). Fitting a barometric density profile yields a temperature of 0.6 MK, while a solar wind-like ({proportional_to}h {sup -2}) density profile yields a density of 1.2 Multiplication-Sign 10{sup 6} cm{sup -3} at an altitude of 1 R{sub S} , assuming harmonic emission. Finally, we found that the solar-cycle-averaged radiated type III energy could be similar in magnitude to that radiated by nanoflares via non-thermal bremsstrahlung processes, and we hint at the possibility that escaping electron beams might carry as much energy away from the corona as is introduced into it by accelerated nanoflare electrons.

  18. Hemolytic C-Type Lectin CEL-III from Sea Cucumber Expressed in Transgenic Mosquitoes Impairs Malaria Parasite Development

    OpenAIRE

    Shigeto Yoshida; Yohei Shimada; Daisuke Kondoh; Yoshiaki Kouzuma; Ghosh, Anil K.; Marcelo Jacobs-Lorena; Sinden, Robert E.

    2007-01-01

    The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and ra...

  19. Bovine type III interferon significantly delays and reduces the severity of foot-and-mouth disease in cattle

    Science.gov (United States)

    Interferons (IFNs) are the first line of defense against viral infections. Although type I and II IFNs have proven effective to inhibit foot-and-mouth disease virus (FMDV) replication in swine, a similar approach has had only limited efficacy in cattle. Recently, a new family of IFNs, type III IFN o...

  20. TEM observations on Type III kerogen, with special reference to coal as a source rock

    Science.gov (United States)

    Liu, Susie Y.; Taylor, Geoff H.

    Type III kerogen follows the coalification track of vitrinite or a bulk coal. It is often inferred that, because this organic matter is of comparatively low hydrogen and high oxygen content, it cannot be more than a marginal source of petroleum. This is not a correct approach because the actual source material is not the whole coal but only a small fraction. Some, at least, of this small fraction appears likely to be just as rich a source as much of Type I or Type II kerogen. There is no doubt that the liptinite macerals are important source materials. However, with TEM it can be shown that there are additional, and in some cases more significant, sources with varying degrees of thermal reactivity. These include: -in vitrinite, the remains of fungi and bacteria, other fine lipid-rich matter, and suberin; -in vitrinitic and especially in inertinitic coal, algal and algae-like material. Micrinite consists of aggregates of very fine spherical bodies which are formed when hydrocarbons are generated. The presence of such aggregates within the coal texture confirms the generative role of the lipid-rich components and provides an important indication as to whether generation has occurred.

  1. Accumulation of properly folded human type III procollagen molecules in specific intracellular membranous compartments in the yeast Pichia pastoris.

    Science.gov (United States)

    Keizer-Gunnink, I; Vuorela, A; Myllyharju, J; Pihlajaniemi, T; Kivirikko, K I; Veenhuis, M

    2000-02-01

    It was recently reported that co-expression of the proalpha1(III) chain of human type III procollagen with the subunits of human prolyl 4-hydroxylase in Pichia pastoris produces fully hydroxylated and properly folded recombinant type III procollagen molecules (Vuorela, A., Myllyharju, J., Nissi, R., Pihlajaniemi, T., Kivirikko, K.I., 1997. Assembly of human prolyl 4-hydroxylase and type III collagen in the yeast Pichia pastoris: formation of a stable enzyme tetramer requires coexpression with collagen and assembly of a stable collagen requires coexpression with prolyl 4-hydroxylase. EMBO J. 16, 6702-6712). These properly folded molecules accumulated inside the yeast cell, however, only approximately 10% were found in the culture medium. We report here that replacement of the authentic signal sequence of the human proalpha1(III) with the Saccharomyces cerevisiae alpha mating factor prepro sequence led only to a minor increase in the amount secreted. Immunoelectron microscopy studies indicated that the procollagen molecules accumulate in specific membranous vesicular compartments that are closely associated with the nuclear membrane. Prolyl 4-hydroxylase, an endoplasmic reticulum (ER) lumenal enzyme, was found to be located in the same compartments. Non-helical proalpha1(III) chains produced by expression without recombinant prolyl 4-hydroxylase likewise accumulated within these compartments. The data indicate that properly folded recombinant procollagen molecules accumulate within the ER and do not proceed further in the secretory pathway. This may be related to the large size of the procollagen molecule. PMID:10686423

  2. Identification of a novel PROS1 c.1113T -> GG frameshift mutation in a family with mixed type I/type III protein S deficiency

    NARCIS (Netherlands)

    ten Kate, Min Ki; Mulder, Rene; Platteel, Mathieu; Brouwer, Jan-Leendert P.; van der Steege, Gerrit; van der Meer, Jan

    2006-01-01

    We report a family with type I and type III protein S (PS) deficiency, which showed to be phenotypic variants of the same genetic disease. Direct sequencing analysis of the PROS1 gene was performed to establish the genotype. The ratio of protein C antigen and total PS antigen levels (protein C/S rat

  3. FLARE-ASSOCIATED TYPE III RADIO BURSTS AND DYNAMICS OF THE EUV JET FROM SDO/AIA AND RHESSI OBSERVATIONS

    International Nuclear Information System (INIS)

    We present a detailed description of the interrelation between the Type III radio bursts and energetic phenomena associated with the flare activities in active region AR11158 at 07:58 UT on 2011 February 15. The timing of the Type III radio burst measured by the radio wave experiment on Wind/WAVE and an array of ground-based radio telescopes coincided with an extreme-ultraviolet (EUV) jet and hard X-ray (HXR) emission observed by SDO/AIA and RHESSI, respectively. There is clear evidence that the EUV jet shares the same source region as the HXR emission. The temperature of the jet, as determined by multiwavelength measurements by Atmospheric Imaging Assembly, suggests that Type III emission is associated with hot, 7 MK, plasma at the jet's footpoint.

  4. Evidence for four- and three-wave interactions in solar type III radio emissions

    Directory of Open Access Journals (Sweden)

    G. Thejappa

    2013-08-01

    Full Text Available The high time resolution observations obtained by the STEREO/WAVES experiment show that in the source regions of solar type III radio bursts, Langmuir waves often occur as intense localized wave packets with short durations of only few ms. One of these wave packets shows that it is a three-dimensional field structure with WLneTe ~ 10−3, where WL is the peak energy density, and ne and Te are the electron density and temperature, respectively. For this wave packet, the conditions of the oscillating two-stream instability (OTSI and supersonic collapse are satisfied within the error range of determination of main parameters. The density cavity, observed during this wave packet indicates that its depth, width and temporal coincidence are consistent with those of a caviton, generated by the ponderomotive force of the collapsing wave packet. The spectrum of each of the parallel and perpendicular components of the wave packet contains a primary peak at fpe, two secondary peaks at fpe ± fS and a low-frequency enhancement below fS, which, as indicated by the frequency and wave number resonance conditions, and the fast Fourier transform (FFT-based tricoherence spectral peak at (fpe, fpe, fpe + fS, fpe − fS, are coupled to each other by the OTSI type of four-wave interaction (fpe is the local electron plasma frequency and fS is the frequency of ion sound waves. In addition to the primary peak at fpe, each of these spectra also contains a peak at 2fpe, which as indicated by the frequency and wave number resonance conditions, and the wavelet-based bicoherence spectral peak at (fpe, fpe, appears to correspond to the second harmonic electromagnetic waves generated as a result of coalescence of oppositely propagating sidebands excited by the OTSI. Thus, these observations for the first time provide combined evidence that (1 the OTSI and related strong turbulence processes play a significant role in the stabilization of the electron beam, (2 the coalescence

  5. Activation of type III interferon genes by pathogenic bacteria in infected epithelial cells and mouse placenta.

    Directory of Open Access Journals (Sweden)

    Hélène Bierne

    Full Text Available Bacterial infections trigger the expression of type I and II interferon genes but little is known about their effect on type III interferon (IFN-λ genes, whose products play important roles in epithelial innate immunity against viruses. Here, we studied the expression of IFN-λ genes in cultured human epithelial cells infected with different pathogenic bacteria and in the mouse placenta infected with Listeria monocytogenes. We first showed that in intestinal LoVo cells, induction of IFN-λ genes by L. monocytogenes required bacterial entry and increased further during the bacterial intracellular phase of infection. Other Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis, also induced IFN-λ genes when internalized by LoVo cells. In contrast, Gram-negative bacteria Salmonella enterica serovar Typhimurium, Shigella flexneri and Chlamydia trachomatis did not substantially induce IFN-λ. We also found that IFN-λ genes were up-regulated in A549 lung epithelial cells infected with Mycobacterium tuberculosis and in HepG2 hepatocytes and BeWo trophoblastic cells infected with L. monocytogenes. In a humanized mouse line permissive to fetoplacental listeriosis, IFN-λ2/λ3 mRNA levels were enhanced in placentas infected with L. monocytogenes. In addition, the feto-placental tissue was responsive to IFN-λ2. Together, these results suggest that IFN-λ may be an important modulator of the immune response to Gram-positive intracellular bacteria in epithelial tissues.

  6. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

    Science.gov (United States)

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-01-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  7. The type III protein secretion system contributes to Xanthomonas citri subsp. citri biofilm formation

    KAUST Repository

    Zimaro, Tamara

    2014-04-18

    Background: Several bacterial plant pathogens colonize their hosts through the secretion of effector proteins by a Type III protein secretion system (T3SS). The role of T3SS in bacterial pathogenesis is well established but whether this system is involved in multicellular processes, such as bacterial biofilm formation has not been elucidated. Here, the phytopathogen Xanthomonas citri subsp. citri (X. citri) was used as a model to gain further insights about the role of the T3SS in biofilm formation. Results: The capacity of biofilm formation of different X. citri T3SS mutants was compared to the wild type strain and it was observed that this secretion system was necessary for this process. Moreover, the T3SS mutants adhered proficiently to leaf surfaces but were impaired in leaf-associated growth. A proteomic study of biofilm cells showed that the lack of the T3SS causes changes in the expression of proteins involved in metabolic processes, energy generation, exopolysaccharide (EPS) production and bacterial motility as well as outer membrane proteins. Furthermore, EPS production and bacterial motility were also altered in the T3SS mutants. Conclusions: Our results indicate a novel role for T3SS in X. citri in the modulation of biofilm formation. Since this process increases X. citri virulence, this study reveals new functions of T3SS in pathogenesis. 2014 Zimaro et al.; licensee BioMed Central Ltd.

  8. Biomechanical Study Using the Finite Element Method of Internal Fixation in Pauwels Type III Vertical Femoral Neck Fractures

    Directory of Open Access Journals (Sweden)

    Noda

    2015-08-01

    Full Text Available Background Several factors are known to influence osseous union of femoral neck fractures. Numerous clinical studies have reported different results, hence with different recommendations regarding treatment of Pauwels III fractures: femoral neck fractures with a more vertically oriented fracture line. The current study aimed to analyze biomechanically whether this fracture poses a higher risk of nonunion. Objectives To analyze the influence of one designated factor, authors believe that a computerized fracture model, using a finite element Finite Element Method (FEM, may be essential to negate the influence of other factors. The current study aimed to investigate a single factor, i.e. orientation of the fracture line toward a horizontal line, represented by Pauwels classification. It was hypothesized that a model with a vertically oriented fracture line maintaining parity of all other related factors has a higher stress at the fracture site, which would delay fracture healing. This result can be applicable to other types of pinning. Patients and Methods The finite element models were constructed from computed tomography data of the femur. Three fracture models, treated with pinning, were constructed based on Pauwels classification: Type I, 30° between the fracture line and a horizontal line; Type II, 50°; and Type III, 70°. All other factors were matched between the models. The Von Mises stress and principal stress distribution were examined along with the fracture line in each model. Results The peak Von Mises stresses at the medial femoral neck of the fracture site were 35, 50 and 130 MPa in Pauwels type I, II, and III fractures, respectively. Additionally, the peak Von Mises stresses along with the fracture site at the lateral femoral neck were 140, 16, and 8 MPa in Pauwels type I, II, and III fractures, respectively. The principal stress on the medial femoral neck in Pauwels type III fracture was identified as a traction stress, whereas

  9. Strains of the Propionibacterium acnes type III lineage are associated with the skin condition progressive macular hypomelanosis

    Science.gov (United States)

    Barnard, Emma; Liu, Jared; Yankova, Eliza; Cavalcanti, Silvana M.; Magalhães, Marcelo; Li, Huiying; Patrick, Sheila; McDowell, Andrew

    2016-01-01

    Progressive macular hypomelanosis (PMH) is a common skin disorder that causes hypopigmentation in a variety of skin types. Although the underlying aetiology of this condition is unclear, there is circumstantial evidence that links the skin bacterium Propionibacterium acnes to the condition. We now describe the first detailed population genetic analysis of P. acnes isolates recovered from paired lesional and non-lesional skin of PMH patients. Our results demonstrate a strong statistical association between strains from the type III phylogenetic lineage and PMH lesions (P = 0.0019), but not those representing other phylogroups, including those associated with acne (type IA1). We also demonstrate, based on in silico 16S rDNA analysis, that PMH isolates previously recovered from patients in Europe are also consistent with the type III lineage. Using comparative genome analysis, we identified multiple genomic regions that are specific for, or absent from, type III strains compared to other phylogroups. In the former case, these include open reading frames with putative functions in metabolism, transport and transcriptional regulation, as well as predicted proteins of unknown function. Further study of these genomic elements, along with transcriptional and functional analyses, may help to explain why type III strains are associated with PMH. PMID:27555369

  10. Oblique Axis Body Fracture: An Unstable Subtype of Anderson Type III Odontoid Fractures—Apropos of Two Cases

    Directory of Open Access Journals (Sweden)

    Hirokazu Takai

    2016-01-01

    Full Text Available Purpose. Anderson type III odontoid fractures have traditionally been considered stable and treated conservatively. However, unstable cases with unfavorable results following conservative treatment have been reported. Methods. We present the cases of two patients who sustained minimally displaced Anderson type III fractures with a characteristic fracture pattern that we refer to as “oblique type axis body fracture.” Results. The female patients aged 90 and 72 years, respectively, were both diagnosed with minimally displaced Anderson type III fractures. Both fractures had a characteristic “oblique type” fracture pattern. The first patient was treated conservatively with cervical spine immobilization in a semirigid collar. However, gross displacement was noted at the 6-week follow-up visit. The second patient was therefore treated operatively by C1–C3/4 posterior fusion and the course was uneventful. Conclusions. Oblique type axis body fractures resemble a highly unstable subtype of Anderson type III fractures with the potential of severe secondary deformity following conservative treatment, irrespective of initial grade of displacement. The authors therefore warrant a high index of suspicion for this injury and suggest early operative stabilization.

  11. Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, C.E.; Taylor, P.E.; Zang, E.A.; Morrison, J.M.; Harley, E.J.; de Cordoba, S.R.; Bacino, C.; Ting, R.C.; Bodner, A.J.; Sarngadharan, M.G.; Gallo, R.C.

    1986-04-25

    Using blood samples collected since 1978, the authors investigated the epidemiology of human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome, in a group of 378 homosexually active men who have resided in New York City since the acquire immunodeficiency syndrome epidemic began. The anti-HTLV-III prevalence was 6.6% in sera from 1978 or 1979, and the subsequent annual incidence of seroconversion among susceptible men ranged between 5.5% and 10.6%. The highest incidences were in recent years, even though these men reported a decrease in their sexual activity during this time. These data demonstrate the continuing risk of HTLV-III infections in the homosexual population studied and emphasize the need for more effective prevention of transmission. The year during which antibody was first present was the only factor identified that was associated with altered cell-mediated immunity in antibody-positive men.

  12. Ulysses Observations of Nonlinear Wave-wave Interactions in the Source Regions of Type III Solar Radio Bursts

    Indian Academy of Sciences (India)

    G. Thejappa; R. J. MacDowall

    2000-09-01

    The Ulysses Unified Radio and Plasma Wave Experiment (URAP) has observed Langmuir, ion-acoustic and associated solar type III radio emissions in the interplanetary medium. Bursts of 50-300 Hz (in the spacecraft frame) electric field signals, corresponding to long-wavelength ion-acoustic waves are often observed coincident in time with the most intense Langmuir wave spikes, providing evidence for the electrostatic decay instability. Langmuir waves often occur as envelope solitons, suggesting that strong turbulence processes, such as modulational instability and soliton formation, often coexist with weak turbulence processes, such as electrostatic decay, in a few type III burst source regions.

  13. Epigenetic acquisition of inducibility of type III cytotoxicity in P. aeruginosa

    Directory of Open Access Journals (Sweden)

    Guery Benoit

    2006-05-01

    Full Text Available Abstract Background Pseudomonas aeruginosa, an opportunistic pathogen, is often encountered in chronic lung diseases such as cystic fibrosis or chronic obstructive pneumonia, as well as acute settings like mechanical ventilation acquired pneumonia or neutropenic patients. It is a major cause of mortality and morbidity in these diseases. In lungs, P. aeruginosa settles in a biofilm mode of growth with the secretion of exopolysaccharides in which it is encapsulated, enhancing its antibiotic resistance and contributing to the respiratory deficiency of patients. However, bacteria must first multiply to a high density and display a cytotoxic phenotype to avoid the host's defences. A virulence determinant implicated in this step of infection is the type III secretion system (TTSS, allowing toxin injection directly into host cells. At the beginning of the infection, most strains isolated from patients' lungs possess an inducible TTSS allowing toxins injection or secretion upon in vivo or in vitro activation signals. As the infection persists most of the bacteria permanently loose this capacity, although no mutations have been evidenced. We name "non inducible" this phenotype. As suggested by the presence of a positive feedback circuit in the regulatory network controlling TTSS expression, it may be due to an epigenetic switch allowing heritable phenotypic modifications without genotype's mutations. Results Using the generalised logical method, we designed a minimal model of the TTSS regulatory network that could support the epigenetic hypothesis, and studied its dynamics which helped to define a discriminating experimental scenario sufficient to validate the epigenetic hypothesis. A mathematical framework based on formal methods from computer science allowed a rigorous validation and certification of parameters of this model leading to epigenetic behaviour. Then, we demonstrated that a non inducible strain of P. aeruginosa can stably acquire the

  14. In silico identification of potential chaperone genes that belong to type III and type IV secretion systems in Xanthomonas axonopodis pv citri

    Directory of Open Access Journals (Sweden)

    Letícia Khater

    2005-01-01

    Full Text Available The secretion of bacterial virulence factors and flagellar components requires the assistance of specific type III and flagellar chaperones. Standard computational annotation of the genome of Xanthomonas axonopodis pv citri, a plant pathogen that causes citrus canker, initially did not identify any genes belonging to these chaperone categories since the primary sequence homology between them was very low. However, in a search for hypothetical proteins with characteristics similar to these chaperones, we have now identified 30 chromosomal and 10 plasmidial potential genes encoding chaperones belonging to types III/IV, and flagellar secretion systems in this organism. The significance of these findings is discussed.

  15. A modeling study of notch noise responses of type III units in the gerbil dorsal cochlear nucleus.

    Science.gov (United States)

    Zheng, Xiaohan; Voigt, Herbert F

    2006-12-01

    A computational model of the neural circuitry of the gerbil dorsal cochlear nucleus (DCN), based on the MacGregor's neuromime model, was used to simulate type III unit (P-cell) responses to notch noise stimuli. The DCN patch model is based on a previous computational model of the cat DCN [Hancock, K. E., and H. F. Voigt. Ann. Biomed. Eng. 27:73-87, 1999]. According to the experimental study of Parsons et al. [Ann. Biomed. Eng. 29:887-896, 2001], the responses of gerbil DCN type III units to notch noise stimuli are similar to those of cat DCN type IV units, which are thought to be spectral notch detectors. This suggests that type III units in the gerbil DCN may serve as spectral notch detectors. In this modeling study, a simplified notch noise response plot--spike discharge rate vs. notch cutoff frequency plot--was used to compare model responses to the experimental results. Parameter estimation and sensitivity analysis of three connection parameters within the DCN patch have been studied and shows the model is robust, providing reasonable fits to the experimental data from 14 of 15 type III units examined.

  16. Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III

    Directory of Open Access Journals (Sweden)

    Schiöth Helgi B

    2011-07-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA type I, II and III is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (SMN1. SMN2 is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two SMN2 copies while most SMA type II patients carry three SMN2 copies and SMA III patients have three or four SMN2 copies. The SMN1 gene produces a full-length transcript (FL-SMN while SMN2 is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA. Methods In this study we performed quantification of the SMN2 gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the SMN1 gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker. Results Comparison of the SMN2 copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III and presence of four copies of the SMN2 gene. In both asymptomatic cases we found an increased number of SMN2 copies in the healthy carriers and a biallelic SMN1 absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls. Conclusions We suggest that the SMN2 gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.

  17. Chronic effects of a Salmonella type III secretion effector protein AvrA in vivo.

    Directory of Open Access Journals (Sweden)

    Rong Lu

    Full Text Available BACKGROUND: Salmonella infection is a common public health problem that can become chronic and increase the risk of inflammatory bowel diseases and cancer. AvrA is a Salmonella bacterial type III secretion effector protein. Increasing evidence demonstrates that AvrA is a multi-functional enzyme with critical roles in inhibiting inflammation, regulating apoptosis, and enhancing proliferation. However, the chronic effects of Salmonella and effector AvrA in vivo are still unknown. Moreover, alive, mutated, non-invasive Salmonella is used as a vector to specifically target cancer cells. However, studies are lacking on chronic infection with non-pathogenic or mutated Salmonella in the host. METHODS/PRINCIPAL FINDINGS: We infected mice with Salmonella Typhimurium for 27 weeks and investigated the physiological effects as well as the role of AvrA in intestinal inflammation. We found altered body weight, intestinal pathology, and bacterial translocation in spleen, liver, and gallbladder in chronically Salmonella-infected mice. Moreover, AvrA suppressed intestinal inflammation and inhibited the secretion of cytokines IL-12, IFN-gamma, and TNF-alpha. AvrA expression in Salmonella enhanced its invasion ability. Liver abscess and Salmonella translocation in the gallbladder were observed and may be associated with AvrA expression in Salmonella. CONCLUSION/SIGNIFICANCE: We created a mouse model with persistent Salmonella infection in vivo. Our study further emphasizes the importance of the Salmonella effector protein AvrA in intestinal inflammation, bacterial translocation, and chronic infection in vivo.

  18. Particle-In-Cell, self-consistent electromagnetic wave emission simulations of type III radio bursts

    CERN Document Server

    Tsiklauri, David

    2010-01-01

    High-resolution, 1.5D Particle-in-Cell, relativistic, fully electromagnetic simulations are used to model electromagnetic wave emission generation in the context of solar type III radio bursts. The model studies generation of electromagnetic waves by a super-thermal, hot beam of electrons injected into a plasma thread that contains uniform longitudinal magnetic field and a parabolic density gradient. In effect, a single magnetic line connecting Sun to earth is considered, for which four cases are studied. (i) We find that the physical system without a beam is stable and only low amplitude level electromagnetic drift waves (noise) are excited. (ii) The beam injection direction is controlled by setting either longitudinal or oblique electron initial drift speed, i.e. by setting the beam pitch angle. In the case of zero pitch angle, the beam excites only electrostatic, standing waves, oscillating at local plasma frequency, in the beam injection spatial location, and only low level electromagnetic drift wave nois...

  19. /sup 31/P-NMR studies of a case of type III glycogenosis

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Mitsuru; Aizawa, Hitoshi; Itoh, Masamitsu; Yoshikawa, Kohki; Murase, Toshio

    1988-05-01

    /sup 31/P-NMR spectra of skeletal muscles were obtained from a patient of type III glycogenosis (33 y.o. man, reported by one of the authors, T. Murase, in 1973) and the control subject (32 y.o. man), using a superconducting whole body MR (Magnetom, Siemens). Two parameters, 1. muscle pH calculated from the chemical shift of Pi (inorganic phosphate) and PCr (creatine phosphate) and 2. PCr/Pi ratio were monitored before and after the aerobic or ischemic exercise. In resting state, the spectra were normal except for the muscle pH of thigh extensors (7.3), which was obviously higher than that of the control subject (7.0). Significant reduction of PCr/Pi ratio (from 7.0 to 4.1) was observed after the aerobic exercise in thigh extensors. Such a reduction was not recognized in the control subject. The ischemic exercise of forearm muscles revealed slight decrease in muscle pH (from 7.1 to 6.9), which was less prominent than that of the control subject. These results were compatible with the abnormality in the energy metabolism of this disorder, the block in the pathway of glycogenolysis.

  20. QCD Corrections to Pair Production of Type III Seesaw Leptons at Hadron Colliders

    CERN Document Server

    Ruiz, Richard

    2015-01-01

    If kinematically accessible, hadron collider experiments provide an ideal laboratory for the direct production of heavy lepton partners in Seesaw models. In the context of the Type III Seesaw Mechanism, the $\\mathcal{O}(\\alpha_s)$ rate and shape corrections are presented for the pair production of hypothetical, heavy $SU(2)_L$ triplet leptons in $pp$ collisions at $\\sqrt{s}=13,$ 14, and 100 TeV. The next-to-leading order (NLO) $K$-factors span, approximately, $K^{NLO}=1.1 - 1.4$ for both charged current and neutral current processes over a triplet mass range $m_T = 100~\\text{GeV}-2\\text{TeV}$. Total production cross sections exhibit a $^{+5\\%}_{-6\\%}$ scale dependence at 14 TeV and $\\pm1\\%$ at 100 TeV. The NLO differential $K$-factors for heavy lepton kinematics are largely flat, suggesting that na\\"ive scaling by the total $K^{NLO}$ is reasonably justified. The resummed transverse momentum distribution of the dilepton system is presented at leading logarithmic (LL) accuracy. The effects of resummation are la...

  1. Structure of a bacterial type III secretion system in contact with a host membrane in situ

    Science.gov (United States)

    Nans, Andrea; Kudryashev, Mikhail; Saibil, Helen R.; Hayward, Richard D.

    2015-12-01

    Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. Contact with host membranes is critical for T3SS activation, yet little is known about T3SS architecture in this state or the conformational changes that drive effector translocation. Here we use cryo-electron tomography and sub-tomogram averaging to derive the intact structure of the primordial Chlamydia trachomatis T3SS in the presence and absence of host membrane contact. Comparison of the averaged structures demonstrates a marked compaction of the basal body (4 nm) occurs when the needle tip contacts the host cell membrane. This compaction is coupled to a stabilization of the cytosolic sorting platform-ATPase. Our findings reveal the first structure of a bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking `pump-action' conformational changes that underpin effector injection.

  2. Salmonella Typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells.

    Directory of Open Access Journals (Sweden)

    Vincent M Bruno

    2009-08-01

    Full Text Available Recognition of conserved bacterial products by innate immune receptors leads to inflammatory responses that control pathogen spread but that can also result in pathology. Intestinal epithelial cells are exposed to bacterial products and therefore must prevent signaling through innate immune receptors to avoid pathology. However, enteric pathogens are able to stimulate intestinal inflammation. We show here that the enteric pathogen Salmonella Typhimurium can stimulate innate immune responses in cultured epithelial cells by mechanisms that do not involve receptors of the innate immune system. Instead, S. Typhimurium stimulates these responses by delivering through its type III secretion system the bacterial effector proteins SopE, SopE2, and SopB, which in a redundant fashion stimulate Rho-family GTPases leading to the activation of mitogen-activated protein (MAP kinase and NF-kappaB signaling. These observations have implications for the understanding of the mechanisms by which Salmonella Typhimurium induces intestinal inflammation as well as other intestinal inflammatory pathologies.

  3. The structural and optical properties of type III human collagen biosynthetic corneal substitutes.

    Science.gov (United States)

    Hayes, Sally; Lewis, Phillip; Islam, M Mirazul; Doutch, James; Sorensen, Thomas; White, Tomas; Griffith, May; Meek, Keith M

    2015-10-01

    The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2-methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2-9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. PMID:26159106

  4. Variation of Langmuir wave polarization with electron beam speed in type III radio bursts

    International Nuclear Information System (INIS)

    Observations by the twin STEREO spacecraft of in-situ electric field waveforms and radio signatures associated with type III radio bursts have demonstrated that the polarization of electron beam-driven waves near the local plasma frequency depends strongly on the speed of the driving electron beam. We expand upon a previous study by including all radio bursts with in-situ waveforms observed by STEREO in 2011. The expanded data set contains five times more radio bursts (35 up from 7) and three times as many Langmuir waves (663 up from 168). While this expanded study supports the results of the original study, that faster (slower) beam electrons drive waves with strong (weak) electric fields perpendicular to the local magnetic field, the larger data set emphasizes that the observation of strong perpendicular electric fields at high electron beam speeds is probabilistic rather than definite. This property supports the interpretation of wave polarization dependence on beam speed as Langmuir/z-mode waves shifted to small wave number through interaction with turbulent solar wind density fluctuations.

  5. Serum type III procollagen N-terminal peptide in coal miners.

    Science.gov (United States)

    Janssen, Y M; Engelen, J J; Giancola, M S; Low, R B; Vacek, P; Borm, P J

    1992-01-01

    Health surveillance of workers exposed to fibrogenic agents ideally should identify individuals at risk or detect pulmonary fibrosis in preclinical stages. We investigated serum procollagen type III N-terminal peptide (PIIIP) in several groups of active miners and in a nondust-exposed control group. The purpose of this study was to determine the applicability of PIIIP as an early noninvasive marker of pulmonary fibrosis in workers exposed to coal mine dust. PIIIP levels were significantly elevated in miners without radiological signs of coal workers pneumoconiosis (CWP) as compared with the nonexposed controls. However, in coal miners with CWP beyond ILO classification 1/0, PIIIP levels were not significantly different from nondust-exposed controls. Trend analysis within the miners group indicated a decrease in PIIIP levels with progression of the fibrosis. Our data suggest that detection of early lung fibrosis by measuring serum PIIIP values may be more sensitive than radiological diagnosis of CWP. However, follow-up of the control miners with respect to serum PIIIP and chest radiography is essential to validate PIIIP as a biological marker for CWP. PMID:1572317

  6. Neutrino Masses at LHC: Minimal Lepton Flavour Violation in Type-III See-saw

    CERN Document Server

    Eboli, O J P; Gonzalez-Garcia, M C

    2011-01-01

    We study the signatures of minimal lepton flavour violation in a simple Type-III see--saw model in which the flavour scale is given by the new fermion triplet mass and it can be naturally light enough to be produced at the LHC. In this model the flavour structure of the couplings of the triplet fermions to the Standard Model leptons can be reconstructed from the neutrino mass matrix and the smallness of the neutrino mass is associated with a tiny violation of total lepton number. Characteristic signatures of this model include suppressed lepton number violation decays of the triplet fermions, absence of displaced vertices in their decays and predictable lepton flavour composition of the states produced in their decays. We study the observability of these signals in the processes $pp\\rightarrow 3\\ell + 2j +\\Sla{E_T}$ and $pp\\rightarrow 2\\ell + 4j$ with $\\ell =e$ or $\\mu$ taking into account the present low energy data on neutrino physics and the corresponding Standard Model backgrounds. Our results indicate th...

  7. Bile salt receptor complex activates a pathogenic type III secretion system

    Energy Technology Data Exchange (ETDEWEB)

    Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N.; Salomon, Dor; Tomchick, Diana R.; Grishin, Nick V.; Orth, Kim

    2016-07-05

    Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered thatVibrio parahaemolyticusVtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.

  8. Pseudomonas aeruginosa Type III Secretory Toxin ExoU and Its Predicted Homologs

    Directory of Open Access Journals (Sweden)

    Teiji Sawa

    2016-10-01

    Full Text Available Pseudomonas aeruginosa ExoU, a type III secretory toxin and major virulence factor with patatin-like phospholipase activity, is responsible for acute lung injury and sepsis in immunocompromised patients. Through use of a recently updated bacterial genome database, protein sequences predicted to be homologous to Ps. aeruginosa ExoU were identified in 17 other Pseudomonas species (Ps. fluorescens, Ps. lundensis, Ps. weihenstephanensis, Ps. marginalis, Ps. rhodesiae, Ps. synxantha, Ps. libanensis, Ps. extremaustralis, Ps. veronii, Ps. simiae, Ps. trivialis, Ps. tolaasii, Ps. orientalis, Ps. taetrolens, Ps. syringae, Ps. viridiflava, and Ps. cannabina and 8 Gram-negative bacteria from three other genera (Photorhabdus, Aeromonas, and Paludibacterium. In the alignment of the predicted primary amino acid sequences used for the phylogenetic analyses, both highly conserved and nonconserved parts of the toxin were discovered among the various species. Further comparative studies of the predicted ExoU homologs should provide us with more detailed information about the unique characteristics of the Ps. aeruginosa ExoU toxin.

  9. A Decade of Solar Type III Radio Bursts Observed by the Nancay Radioheliograph 1998-2008

    Science.gov (United States)

    Saint-Hilaire, Pascal; Vilmer, N.; Kerdraon, A.

    2013-07-01

    We present a statistical survey of almost 10'000 radio type III bursts observed by the Nancay Radioheliograph from 1998 to 2008, covering nearly a full solar cycle. In particular, sources sizes, positions, and fluxes were examined. We find an east-west asymmetry in source positions that could be attributed to a ~6 degrees eastward tilt of the magnetic field, that source FWHM sizes s roughly follow a solar-cycle-averaged distribution dN/ds = 14 ν-3.3s-4 arcmin-1 day-1, and that source fluxes closely follow a solar-cycle-averaged dN/dS = 0.34 ν-2.9 S-1.7 sfu-1 day-1 distribution (when ν is in GHz, s in arcminutes, and S in sfu). Fitting a barometric density profile yields a temperature of 0.6 MK, while a solar wind-like h-2) density profile yields a density of 1.2 × 106 cm-3 at an altitude of 1 Rs, assuming harmonic emission. Finally, the flux distribution combined with rough radiative efficiency estimates hint at the possibility that escaping electron beams might carry as much energy away from the corona as is introduced into it by nanoflare-accelerated electrons.

  10. Phase Coupling Between Spectral Components of Collapsing Langmuir Solitons in Solar Type III Radio Bursts

    Science.gov (United States)

    Thejappa, G.; MacDowall, R. J.; Bergamo, M.

    2012-01-01

    We present the high time resolution observations of one of the Langmuir wave packets obtained in the source region of a solar type III radio burst. This wave packet satisfies the threshold condition of the supersonic modulational instability, as well as the criterion of a collapsing Langmuir soliton, i.e., the spatial scale derived from its peak intensity is less than that derived from its short time scale. The spectrum of t his wave packet contains an intense spectral peak at local electron plasma frequency, f(sub pe) and relatively weaker peaks at 2f(sub pe) and 3f(sub pe). We apply the wavelet based bispectral analysis technique on this wave packet and compute the bicoherence between its spectral components. It is found that the bicoherence exhibits two peaks at (approximately f(sub pe), approximately f(sub pe)) and (approximately f(sub pe) approximately 2f(sub pe)), which strongly suggest that the spectral peak at 2f(sub pe) probably corresponds to the second harmonic radio emission, generated as a result of the merging of antiparallel propagating Langmuir waves trapped in the collapsing Langmuir soliton, and, the spectral peak at 3f(sub pe) probably corresponds to the third harmonic radio emission, generated as a result of merging of a trapped Langmuir wave and a second harmonic electromagnetic wave.

  11. Type III effector activation via nucleotide binding, phosphorylation, and host target interaction.

    Directory of Open Access Journals (Sweden)

    Darrell Desveaux

    2007-03-01

    Full Text Available The Pseudomonas syringae type III effector protein avirulence protein B (AvrB is delivered into plant cells, where it targets the Arabidopsis RIN4 protein (resistance to Pseudomonas maculicula protein 1 [RPM1]-interacting protein. RIN4 is a regulator of basal host defense responses. Targeting of RIN4 by AvrB is recognized by the host RPM1 nucleotide-binding leucine-rich repeat disease resistance protein, leading to accelerated defense responses, cessation of pathogen growth, and hypersensitive host cell death at the infection site. We determined the structure of AvrB complexed with an AvrB-binding fragment of RIN4 at 2.3 A resolution. We also determined the structure of AvrB in complex with adenosine diphosphate bound in a binding pocket adjacent to the RIN4 binding domain. AvrB residues important for RIN4 interaction are required for full RPM1 activation. AvrB residues that contact adenosine diphosphate are also required for initiation of RPM1 function. Nucleotide-binding residues of AvrB are also required for its phosphorylation by an unknown Arabidopsis protein(s. We conclude that AvrB is activated inside the host cell by nucleotide binding and subsequent phosphorylation and, independently, interacts with RIN4. Our data suggest that activated AvrB, bound to RIN4, is indirectly recognized by RPM1 to initiate plant immune system function.

  12. Ultradiscrete limit of Bessel function type solutions of the Painlev\\'{e} III equation

    OpenAIRE

    Isojima, Shin

    2014-01-01

    An ultradiscrete analog of the Bessel function is constructed by taking the ultradiscrete limit for a $q$-difference analog of the Bessel function. Then, a direct relationship between a class of special solutions for the ultradiscrete Painlev\\'{e} III equation and those of the discrete Painlev\\'{e} III equation which have a determinantal structure is established.

  13. QCD corrections to pair production of Type III Seesaw leptons at hadron colliders

    Science.gov (United States)

    Ruiz, Richard

    2015-12-01

    If kinematically accessible, hadron collider experiments provide an ideal laboratory for the direct production of heavy lepton partners in Seesaw models. In the context of the Type III Seesaw Mechanism, the O({α}_s) rate and shape corrections are presented for the pair production of hypothetical, heavy SU(2) L triplet leptons in pp collisions at √{s} = 13, 14 and 100TeV. The next-to-leading order (NLO) K-factors span, approximately, K NLO = 1 .1 - 1 .4 for both charged current and neutral current processes over a triplet mass range m T = 100 GeV - 2 TeV. Total production cross sections exhibit a - 6 % + 5 % scale dependence at 14 TeV and ±1% at 100 TeV. The NLO differential K-factors for heavy lepton kinematics are largely flat, suggesting that na¨ıve scaling by the total K NLO is reasonably justified. The resummed transverse momentum distribution of the dilepton system is presented at leading logarithmic (LL) accuracy. The effects of resummation are large in TeV-scale dilepton systems. Discovery potential to heavy lepton pairs at 14 and 100 TeV is briefly explored: at the High-Luminosity LHC, we estimate a 4 .8 - 6 .3 σ discovery potential maximally for m T = 1 .5 - 1 .6 TeV after 3000 fb-1. With 300 (3000) fb-1, there is 2σ sensitivity up to m T = 1 .3 - 1 .4 TeV (1 .7 - 1 .8 TeV) in the individual channels. At 100 TeV and with 10 fb-1, a 5 σ discovery can be achieved for m T = 1 .4 - 1 .6 TeV. Due to the factorization properties of Drell-Yan-type systems, the fixed order and resummed calculations reduce to convolutions over tree-level quantities.

  14. The Architecture of the Cytoplasmic Region of Type III Secretion Systems

    Science.gov (United States)

    Makino, Fumiaki; Shen, Dakang; Kajimura, Naoko; Kawamoto, Akihiro; Pissaridou, Panayiota; Oswin, Henry; Pain, Maria; Murillo, Isabel; Namba, Keiichi; Blocker, Ariel J.

    2016-01-01

    Type III secretion systems (T3SSs) are essential devices in the virulence of many Gram-negative bacterial pathogens. They mediate injection of protein effectors of virulence from bacteria into eukaryotic host cells to manipulate them during infection. T3SSs involved in virulence (vT3SSs) are evolutionarily related to bacterial flagellar protein export apparatuses (fT3SSs), which are essential for flagellar assembly and cell motility. The structure of the external and transmembrane parts of both fT3SS and vT3SS is increasingly well-defined. However, the arrangement of their cytoplasmic and inner membrane export apparatuses is much less clear. Here we compare the architecture of the cytoplasmic regions of the vT3SSs of Shigella flexneri and the vT3SS and fT3SS of Salmonella enterica serovar Typhimurium at ~5 and ~4 nm resolution using electron cryotomography and subtomogram averaging. We show that the cytoplasmic regions of vT3SSs display conserved six-fold symmetric features including pods, linkers and an ATPase complex, while fT3SSs probably only display six-fold symmetry in their ATPase region. We also identify other morphological differences between vT3SSs and fT3SSs, such as relative disposition of their inner membrane-attached export platform, C-ring/pods and ATPase complex. Finally, using classification, we find that both types of apparatuses can loose elements of their cytoplasmic region, which may therefore be dynamic. PMID:27686865

  15. BACE1 Processing of NRG1 Type III Produces a Myelin-Inducing Signal but Is Not Essential for the Stimulation of Myelination

    OpenAIRE

    Velanac, Viktorija; Unterbarnscheidt, Tilmann; Hinrichs, Wilko; Gummert, Maike N.; Fischer, Tobias M; Rossner, Moritz J.; Trimarco, Amelia; Brivio, Veronica; Taveggia, Carla; Willem, Michael; Haass, Christian; Möbius, Wiebke; Nave, Klaus-Armin; Schwab, Markus H

    2011-01-01

    Myelin sheath thickness is precisely adjusted to axon caliber, and in the peripheral nervous system, neuregulin 1 (NRG1) type III is a key regulator of this process. It has been proposed that the protease BACE1 activates NRG1 dependent myelination. Here, we characterize the predicted product of BACE1-mediated NRG1 type III processing in transgenic mice. Neuronal overexpression of a NRG1 type III-variant, designed to mimic prior cleavage in the juxtamembrane stalk region, induces hypermyelinat...

  16. Periodic solutions of multispecies-competition predator-prey system with Holling's type III functional response and prey supplement

    Directory of Open Access Journals (Sweden)

    Jiwei He

    2007-07-01

    Full Text Available In this paper, we consider a nonautonomous multispecies competition predator-prey system with Holling's type III functional response and prey supplement. It is proved that the system is uniformly persistent under some conditions. Furthermore, we show that the system has a unique positive periodic solution which is globally asymptotically stable.

  17. A note on classification of proper homothetic vector fields in Kantowski-Sachs and Bianchi type III Lorentzian manifolds

    CERN Document Server

    Shabbir, Ghulam

    2011-01-01

    A complete study of Kantowski-Sachs and Bianchi type III space-times according to their proper homothetic vector fields is given by using direct integration technique. Using the above mentioned technique we have shown that very special classes of the above space-times admit proper homothetic vector fields. The dimension of homothetic vector fields is five.

  18. Complete Genome Sequence of Streptococcus agalactiae Serotype III, Multilocus Sequence Type 283 Strain SG-M1

    OpenAIRE

    Kurosh S. Mehershahi; Hsu, Li Yang; Koh, Tse Hsien; Chen, Swaine L.

    2015-01-01

    Streptococcus agalactiae (group B Streptococcus) is a common commensal strain in the human gastrointestinal tract that can also cause invasive disease in humans and other animals. We report here the complete genome sequence of S. agalactiae SG-M1, a serotype III, multilocus sequence type 283 strain, isolated from a Singaporean patient suffering from meningitis.

  19. Complete Genome Sequence of Streptococcus agalactiae Serotype III, Multilocus Sequence Type 283 Strain SG-M1.

    Science.gov (United States)

    Mehershahi, Kurosh S; Hsu, Li Yang; Koh, Tse Hsien; Chen, Swaine L

    2015-01-01

    Streptococcus agalactiae (group B Streptococcus) is a common commensal strain in the human gastrointestinal tract that can also cause invasive disease in humans and other animals. We report here the complete genome sequence of S. agalactiae SG-M1, a serotype III, multilocus sequence type 283 strain, isolated from a Singaporean patient suffering from meningitis. PMID:26494662

  20. Ubiquity of Putative Type III Secretion Genes among Clinical and Environmental Burkholderia pseudomallei Isolates in Northern Australia

    OpenAIRE

    Smith-Vaughan, H C; Gal, D; Lawrie, P. M.; Winstanley, C.; Sriprakash, K S; Currie, B. J.

    2003-01-01

    Horseradish peroxidase-like type III secretion (TTS1) genes were present in all 116 Northern Australian Burkholderia pseudomallei isolates tested but were not detected in other common environmental Burkholderia species. PCR of TTS1 genes may prove valuable as a diagnostic test.

  1. Hepatic and renal extraction of circulating type III procollagen amino-terminal propeptide and hyaluronan in pig

    DEFF Research Database (Denmark)

    Bentsen, K D; Henriksen, Jens Henrik Sahl; Boesby, S;

    1989-01-01

    Hepatic and renal clearance of the amino-terminal propeptide of type III procollagen (PIIINP) and of the glycosaminoglycan, hyaluronan (HA) were investigated in a catheterization study of seven healthy anesthetized pigs. Two assays were used, in order to distinguish between the metabolism of...

  2. N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone

    Science.gov (United States)

    Context: Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (L...

  3. Talents and Type Iiis: The Effects of the Talents Unlimited Model on Creative Productivity in Gifted Youngsters

    Science.gov (United States)

    Newman, Jane L.

    2005-01-01

    This study examined a set of lessons that integrate the Talents Unlimited Model (TU; C. L. Schlichter, 1986) with the 10 steps of completing a Type III activity (J. S. Renzulli & S. M. Reis, 1985) to determine the effects of these lessons on the quality of students' creative products and on the number of students who completed their products.…

  4. Upregulation of heme oxygenase and collagen type III in the rat bladder after partial bladder outlet obstruction.

    Science.gov (United States)

    Inaba, Mitsuhiko; Ukimura, Osamu; Yaoi, Takeshi; Kawauchi, Akihiro; Fushiki, Shinji; Miki, Tsuneharu

    2007-01-01

    The objective of the study was to evaluate possible changes of the gene expression and localization of the enzymes, heme oxygenase and nitric oxide synthase (NOS), with reference to increase of collagen type III in response to the partial obstruction of the bladder. Following initial obstruction, whole rat bladders were removed for real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Real-time RT-PCR demonstrated significantly enhanced expression of HO (p < 0.01) and collagen type III (p < 0.001) gene on postoperative day 14. Enhanced expression of NOS gene was seen only on postoperative day 4 (p < 0.01). Immunohistochemistry revealed that immunoreactivity to HO-1 had much in common in neural cells and fibers, although immunoreactivity to HO-2 and iNOS was relatively weak. This study suggested gene expression of HO, especially HO-1, was more dramatically changed than NOS, and was upregulated simultaneously with increase of collagen type III after obstruction. HO systems could be involved in the pathogenesis of bladder dysfunction related to increase of collagen type III after obstruction. PMID:17406140

  5. Why do the Solar Type III Burst emit the maximum of their radio energy around 1 MHz ?

    Science.gov (United States)

    Maksimovic, Milan; Krupar, Vratislav; Kontar, Eduard; Zaslavsky, Arnaud; Pascal, Louis; Reid, Hamish; Lecacheux, Alain; Bonnin, Xavier; Santolik, Ondrej; Vilmer, Nicole

    2014-05-01

    We present a statistical survey of a few hundred of Type III bursts observed from about 100 KHz up to about 400 MHz. When displayed as a function of the frequency, the radio flux exhibits a clear maximum at about 1 MHz. This property, already reported in previous studies, will be described in more details and possible explanations about its origin will be discussed.

  6. The Low-High-Low Trend of Type III Radio Burst Starting Frequencies and Solar Flare Hard X-rays

    CERN Document Server

    Reid, Hamish A S; Kontar, Eduard P

    2014-01-01

    Using simultaneous X-ray and radio observations from solar flares, we investigate the link between the type III radio burst starting frequency and hard X-ray spectral index. For a proportion of events the relation derived between the starting height (frequency) of type III radio bursts and the electron beam velocity spectral index (deduced from X-rays) is used to infer the spatial properties (height and size) of the electron beam acceleration region. Both quantities can be related to the distance travelled before an electron beam becomes unstable to Langmuir waves. To obtain a list of suitable events we considered the RHESSI catalogue of X-ray flares and the Phoenix 2 catalogue of type III radio bursts. From the 200 events that showed both type III and X-ray signatures, we selected 30 events which had simultaneous emission in both wavelengths, good signal to noise in the X-ray domain and > 20 seconds duration. We find that > 50 % of the selected events show a good correlation between the starting frequencies ...

  7. DYNC2H1 mutations cause asphyxiating thoracic dystrophy and short rib-polydactyly syndrome, type III.

    Science.gov (United States)

    Dagoneau, Nathalie; Goulet, Marie; Geneviève, David; Sznajer, Yves; Martinovic, Jelena; Smithson, Sarah; Huber, Céline; Baujat, Geneviève; Flori, Elisabeth; Tecco, Laura; Cavalcanti, Denise; Delezoide, Anne-Lise; Serre, Valérie; Le Merrer, Martine; Munnich, Arnold; Cormier-Daire, Valérie

    2009-05-01

    Jeune asphyxiating thoracic dystrophy (ATD) is an autosomal-recessive chondrodysplasia characterized by short ribs and a narrow thorax, short long bones, inconstant polydactyly, and trident acetabular roof. ATD is closely related to the short rib polydactyly syndrome (SRP) type III, which is a more severe condition characterized by early prenatal expression and lethality and variable malformations. We first excluded IFT80 in a series of 26 fetuses and children belonging to 14 families diagnosed with either ATD or SRP type III. Studying a consanguineous family from Morocco, we mapped an ATD gene to chromosome 11q14.3-q23.1 in a 20.4 Mb region and identified homozygous mutations in the cytoplasmic dynein 2 heavy chain 1 (DYNC2H1) gene in the affected children. Compound heterozygosity for DYNC2H1 mutations was also identified in four additional families. Among the five families, 3/5 were diagnosed with ATD and 2/5 included pregnancies terminated for SRP type III. DYNC2H1 is a component of a cytoplasmic dynein complex and is directly involved in the generation and maintenance of cilia. From this study, we conclude that ATD and SRP type III are variants of a single disorder belonging to the ciliopathy group.

  8. Structure-based engineering of a plant type III polyketide synthase: formation of an unnatural nonaketide naphthopyrone.

    Science.gov (United States)

    Abe, Ikuro; Morita, Hiroyuki; Oguro, Satoshi; Noma, Hisashi; Wanibuchi, Kiyofumi; Kawahara, Nobuo; Goda, Yukihiro; Noguchi, Hiroshi; Kohno, Toshiyuki

    2007-05-01

    Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant-specific type III polyketide synthase (PKS) that produces 5,7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA. On the basis of the crystal structures of wild-type and M207G mutant PCS, the F80A/Y82A/M207G triple mutant was constructed and shown to produce an unnatural novel nonaketide naphthopyrone by sequential condensations of nine molecules of malonyl-CoA. This is the first demonstration of the formation of a nonaketide by the structurally simple type III PKS. A homology model predicted that the active-site cavity volume of the triple mutant is increased to 4 times that of the wild-type PCS. PMID:17439126

  9. The low-high-low trend of type III radio burst starting frequencies and solar flare hard X-rays

    Science.gov (United States)

    Reid, Hamish A. S.; Vilmer, Nicole; Kontar, Eduard P.

    2014-07-01

    Aims: Using simultaneous X-ray and radio observations from solar flares, we investigate the link between the type III radio burst starting frequency and hard X-ray spectral index. For a proportion of events the relation derived between the starting height (frequency) of type III radio bursts and the electron beam velocity spectral index (deduced from X-rays) is used to infer the spatial properties (height and size) of the electron beam acceleration region. Both quantities can be related to the distance travelled before an electron beam becomes unstable to Langmuir waves. Methods: To obtain a list of suitable events we considered the RHESSI catalogue of X-ray flares and the Phoenix 2 catalogue of type III radio bursts. From the 200 events that showed both type III and X-ray signatures, we selected 30 events which had simultaneous emission in both wavelengths, good signal to noise in the X-ray domain and >20 s duration. Results: We find that >50% of the selected events show a good correlation between the starting frequencies of the groups of type III bursts and the hard X-ray spectral indices. A low-high-low trend for the starting frequency of type III bursts is frequently observed. Assuming a background electron density model and the thick target approximation for X-ray observations, this leads to a correlation between starting heights of the type III emission and the beam electron spectral index. Using this correlation we infer the altitude and vertical extents of the flare acceleration regions. We find heights from 183 Mm down to 25 Mm while the sizes range from 13 Mm to 2 Mm. These values agree with previous work that places an extended flare acceleration region high in the corona. We also analyse the assumptions that are required to obtain our estimates and explore possible extensions to our assumed model. We discuss these results with respect to the acceleration heights and sizes derived from X-ray observations alone. Appendices are available in electronic form

  10. Observation of solar radio bursts of type II and III at kilometer wavelengths from Prognoz-8 during STIP Interval XII

    International Nuclear Information System (INIS)

    Type II and type III radio events were observed at low frequencies (2.16 MHz to 114 kHz) by the Prognoz-8 satellite during the period of STIP Interval XII in April and May, 1981, respectively. This review covers briefly a chronology of the sub-megahertz radio events, and where possible their association with both groundbased radio observations and solar flare. (author)

  11. Chromosomal assignments of the genes coding for human types II, III, and IV collagen: a dispersed gene family.

    OpenAIRE

    Solomon, E; Hiorns, L R; Spurr, N; Kurkinen, M.; Barlow, D; Hogan, B L; Dalgleish, R.

    1985-01-01

    The human type II collagen gene, COL2A1, has been assigned to chromosome 12, the type III gene, COL3A1, to chromosome 2, and one of the type IV genes, COL4A1, to chromosome 13. These assignments were made by using cloned genes as probes on Southern blots of DNA from a panel of mouse/human somatic cell hybrids. The two genes of type I collagen, COL1A1 and COL2A1, have been mapped previously to chromosomes 17 and 7, respectively. This family of conserved genes seems therefore to be dispersed th...

  12. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Danielle Cristina Tomaz da [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Lima-Leopoldo, Ana Paula; Leopoldo, André Soares [Departamento de Esportes, Centro de Educação Física e Desportos da Universidade Federal do Espírito Santo (UFES), Vitória, ES (Brazil); Campos, Dijon Henrique Salomé de; Nascimento, André Ferreira do [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Oliveira, Sílvio Assis Junior de [Escola de Fisioterapia da Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil); Padovani, Carlos Roberto [Departamento de Bioestatística do Instituto de Ciências Biológicas da Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil); Cicogna, Antonio Carlos, E-mail: dany.tomaz@gmail.com [Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil)

    2014-02-15

    Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C{sub 15} and Ob{sub 15}) and 30 (C{sub 30} and Ob{sub 30}) consecutive weeks. Obesity was determined by adiposity index. The Ob{sub 15} group was similar to the C{sub 15} group regarding the expression of myocardial collagen type I; however, expression in the Ob{sub 30} group was less than C{sub 30} group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob{sub 30} when compared with Ob{sub 15}. Obesity did not affect collagen type III expression. This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression.

  13. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    International Nuclear Information System (INIS)

    Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C15 and Ob15) and 30 (C30 and Ob30) consecutive weeks. Obesity was determined by adiposity index. The Ob15 group was similar to the C15 group regarding the expression of myocardial collagen type I; however, expression in the Ob30 group was less than C30 group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob30 when compared with Ob15. Obesity did not affect collagen type III expression. This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression

  14. Diagnosing the Source Region of a Solar Burst on 26 September 2011 by Using Microwave Type-III Pairs

    Science.gov (United States)

    Tan, B. L.; Karlický, M.; Mészárosová, H.; Kashapova, L.; Huang, J.; Yan, Y.; Kontar, E. P.

    2016-10-01

    We report a peculiar and interesting train of microwave Type-III pair bursts in the impulsive rising phase of a solar flare on 26 September 2011. The observations include radio spectrometers at frequencies of 0.80 - 2.00 GHz from the Ondřejov radiospectrograph in the Czech Republic (ORSC), hard X-ray from the Ramaty High-Energy Solar Spectroscopic Imager (RHESSI) and Gamma-Ray Burst Monitor onboard the Fermi Space Telescope ( Fermi/GRB), EUV images from the Sun Watcher using APS detectors and image Processing instrument onboard the Project for Onboard Autonomy 2 (SWAP/PROBA2), and magnetograms from the Helioseismic and Magnetic Imager onboard the Solar Dynamic Observatory (SDO/HMI). By using a recently developed method (Tan et al., Res. Astron. Astrophys. 16, 82, 2016a), we diagnosed the plasma density, temperature, plasma-β, magnetic field near the source region, the energy of energetic electrons, and the distance between the acceleration region and the emission start sites of Type-III bursts. From the diagnostics, we find that i) The plasma density, temperature, magnetic field, and the distance between the acceleration region and the emission start sites have almost no obvious variations during the period of Type-III pair trains, while the energy of electrons has an obvious peak value that is consistent with the hard X-ray emission. ii) The plasma-β is much higher than unity, showing a highly dynamic process near the emission start site of Type-III bursts. iii) Although the reversed-slope Type-III branches drift more slowly by one order of magnitude than that of the normal Type-IIIs, the related descending and ascending electrons still could have energy of the same order of magnitude. These facts indicate that both the ascending and descending electrons are possibly accelerated by a similar mechanism and in a small source region. These diagnostics can help us to understand the physics in the source region of solar bursts.

  15. Diagnosing the Source Region of a Solar Burst on 26 September 2011 by Using Microwave Type-III Pairs

    Science.gov (United States)

    Tan, B. L.; Karlický, M.; Mészárosová, H.; Kashapova, L.; Huang, J.; Yan, Y.; Kontar, E. P.

    2016-09-01

    We report a peculiar and interesting train of microwave Type-III pair bursts in the impulsive rising phase of a solar flare on 26 September 2011. The observations include radio spectrometers at frequencies of 0.80 - 2.00 GHz from the Ondřejov radiospectrograph in the Czech Republic (ORSC), hard X-ray from the Ramaty High-Energy Solar Spectroscopic Imager (RHESSI) and Gamma-Ray Burst Monitor onboard the Fermi Space Telescope (Fermi/GRB), EUV images from the Sun Watcher using APS detectors and image Processing instrument onboard the Project for Onboard Autonomy 2 (SWAP/PROBA2), and magnetograms from the Helioseismic and Magnetic Imager onboard the Solar Dynamic Observatory (SDO/HMI). By using a recently developed method (Tan et al., Res. Astron. Astrophys. 16, 82, 2016a), we diagnosed the plasma density, temperature, plasma- β, magnetic field near the source region, the energy of energetic electrons, and the distance between the acceleration region and the emission start sites of Type-III bursts. From the diagnostics, we find that i) The plasma density, temperature, magnetic field, and the distance between the acceleration region and the emission start sites have almost no obvious variations during the period of Type-III pair trains, while the energy of electrons has an obvious peak value that is consistent with the hard X-ray emission. ii) The plasma- β is much higher than unity, showing a highly dynamic process near the emission start site of Type-III bursts. iii) Although the reversed-slope Type-III branches drift more slowly by one order of magnitude than that of the normal Type-IIIs, the related descending and ascending electrons still could have energy of the same order of magnitude. These facts indicate that both the ascending and descending electrons are possibly accelerated by a similar mechanism and in a small source region. These diagnostics can help us to understand the physics in the source region of solar bursts.

  16. Intrinsic and extrinsic regulation of type III secretion gene expression in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Manisha R Diaz

    2011-04-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that is particularly problematic in the healthcare setting where it is a frequent cause of pneumonia, bloodstream, and urinary tract infections. An important determinant of P. aeruginosa virulence is a type III secretion system (T3SS. T3SS-dependent intoxication is a complex process that minimally requires binding of P. aeruginosa to host cells, injection of the cytotoxic effector proteins through the host cell plasma membrane, and induction of T3SS gene expression. The latter process, referred to as contact-dependent expression, involves a well-characterized regulatory cascade that activates T3SS gene expression in response to host cell contact. Although host cell contact is a primary activating signal for T3SS gene expression, the involvement of multiple membrane-bound regulatory systems indicates that additional environmental signals also play a role in controlling expression of the T3SS. These regulatory systems coordinate T3SS gene expression with many other cellular activities including motility, mucoidy, polysaccharide production, and biofilm formation. The signals to which the organism responds are poorly understood but many seem to be coupled to the metabolic state of the cell and integrated within a master circuit that assimilates informational signals from endogenous and exogenous sources. Herein we review progress towards unraveling this complex circuitry, provide analysis of the current knowledge gaps, and highlight potential areas for future studies. Complete understanding of the regulatory networks that control T3SS gene expression will maximize opportunities for the development of strategies to treat P. aeruginosa infections.

  17. Potassium transport of Salmonella is important for type III secretion and pathogenesis.

    Science.gov (United States)

    Liu, Yehao; Ho, Katharina Kim; Su, Jing; Gong, Hao; Chang, Alexander C; Lu, Sangwei

    2013-08-01

    Intracellular cations are essential for the physiology of all living organisms including bacteria. Cations such as potassium ion (K(+)), sodium ion (Na(+)) and proton (H(+)) are involved in nearly all aspects of bacterial growth and survival. K(+) is the most abundant cation and its homeostasis in Escherichia coli and Salmonella is regulated by three major K(+) transporters: high affinity transporter Kdp and low affinity transporters Kup and Trk. Previous studies have demonstrated the roles of cations and cation transport in the physiology of Escherichia coli; their roles in the virulence and physiology of pathogenic bacteria are not well characterized. We have previously reported that the Salmonella K(+) transporter Trk is important for the secretion of effector proteins of the type III secretion system (TTSS) of Salmonella pathogenicity island 1 (SPI-1). Here we further explore the role of Salmonella cation transport in virulence in vitro and pathogenesis in animal models. Impairment of K(+) transport through deletion of K(+) transporters or exposure to the chemical modulators of cation transport, gramicidin and valinomycin, results in a severe defect in the TTSS of SPI-1, and this defect in the TTSS was not due to a failure to regulate intrabacterial pH or ATP. Our results also show that K(+) transporters are critical to the pathogenesis of Salmonella in mice and chicks and are involved in multiple growth and virulence characteristics in vitro, including protein secretion, motility and invasion of epithelial cells. These results suggest that cation transport of the pathogenic bacterium Salmonella, especially K(+) transport, contributes to its virulence in addition to previously characterized roles in maintaining homeostasis of bacteria.

  18. Yeast as a Heterologous Model System to Uncover Type III Effector Function

    Science.gov (United States)

    Popa, Crina; Coll, Núria S.; Valls, Marc; Sessa, Guido

    2016-01-01

    Type III effectors (T3E) are key virulence proteins that are injected by bacterial pathogens inside the cells of their host to subvert cellular processes and contribute to disease. The budding yeast Saccharomyces cerevisiae represents an important heterologous system for the functional characterisation of T3E proteins in a eukaryotic environment. Importantly, yeast contains eukaryotic processes with low redundancy and are devoid of immunity mechanisms that counteract T3Es and mask their function. Expression in yeast of effectors from both plant and animal pathogens that perturb conserved cellular processes often resulted in robust phenotypes that were exploited to elucidate effector functions, biochemical properties, and host targets. The genetic tractability of yeast and its amenability for high-throughput functional studies contributed to the success of this system that, in recent years, has been used to study over 100 effectors. Here, we provide a critical view on this body of work and describe advantages and limitations inherent to the use of yeast in T3E research. “Favourite” targets of T3Es in yeast are cytoskeleton components and small GTPases of the Rho family. We describe how mitogen-activated protein kinase (MAPK) signalling, vesicle trafficking, membrane structures, and programmed cell death are also often altered by T3Es in yeast and how this reflects their function in the natural host. We describe how effector structure–function studies and analysis of candidate targeted processes or pathways can be carried out in yeast. We critically analyse technologies that have been used in yeast to assign biochemical functions to T3Es, including transcriptomics and proteomics, as well as suppressor, gain-of-function, or synthetic lethality screens. We also describe how yeast can be used to select for molecules that block T3E function in search of new antibacterial drugs with medical applications. Finally, we provide our opinion on the limitations of S

  19. Characteristics of Metroxylon sagu resistant starch type III as prebiotic substance.

    Science.gov (United States)

    Zi-Ni, Tan; Rosma, Ahmad; Napisah, Hussin; Karim, Alias A; Liong, Min-Tze

    2015-04-01

    Resistant starch type III (RS3 ) was produced from sago (Metroxylon sagu) and evaluated for its characteristics as a prebiotic. Two RS3 samples designated sago RS and HCl-sago RS contained 35.71% and 68.30% RS, respectively, were subjected to hydrolyses by gastric juice and digestive enzymes and to absorption. Both sago RS and HCl-sago RS were resistant to 180 min hydrolysis by gastric acidity at pH 1 to 4 with less than 0.85% hydrolyzed. Both samples were also resistant toward hydrolysis by gastrointestinal tract enzymes and intestinal absorption with 96.75% and 98.69% of RS3 were recovered respectively after 3.5 h digestion and overnight dialysis at 37 °C. Sago RS3 supported the growth of both beneficial (lactobacilli and Bifidobacteria) and pathogenic microbes (Escherichia coli, Campylobacter coli, and Clostridium perfringens) in the range of 2.60 to 3.91 log10 CFU/mL. Hence, prebiotic activity score was applied to describe the extent to which sago RS3 supports selective growth of the lactobacilli and bifidobacteria strains over pathogenic bacteria. The highest scores were obtained from Bifidobacterium sp. FTDC8943 grown on sago RS (+0.26) and HCl-sago RS (+0.24) followed by L. bulgaricus FTDC1511 grown on sago RS (+0.21). The findings had suggested that sago RS3 has the prebiotic partial characteristics and it is suggested to further assess the suitability of sago RS3 as a prebiotic material.

  20. Multiple Xanthomonas euvesicatoria Type III Effectors Inhibit flg22-Triggered Immunity.

    Science.gov (United States)

    Popov, Georgy; Fraiture, Malou; Brunner, Frederic; Sessa, Guido

    2016-08-01

    Xanthomonas euvesicatoria is the causal agent of bacterial spot disease in pepper and tomato. X. euvesicatoria bacteria interfere with plant cellular processes by injecting effector proteins into host cells through the type III secretion (T3S) system. About 35 T3S effectors have been identified in X. euvesicatoria 85-10, and a few of them were implicated in suppression of pattern-triggered immunity (PTI). We used an Arabidopsis thaliana pathogen-free protoplast-based assay to identify X. euvesicatoria 85-10 effectors that interfere with PTI signaling induced by the bacterial peptide flg22. Of 33 tested effectors, 17 inhibited activation of a PTI-inducible promoter. Among them, nine effectors also interfered with activation of an abscisic acid-inducible promoter. However, effectors that inhibited flg22-induced signaling did not affect phosphorylation of mitogen-activated protein (MAP) kinases acting downstream of flg22 perception. Further investigation of selected effectors revealed that XopAJ, XopE2, and XopF2 inhibited activation of a PTI-inducible promoter by the bacterial peptide elf18 in Arabidopsis protoplasts and by flg22 in tomato protoplasts. The effectors XopF2, XopE2, XopAP, XopAE, XopH, and XopAJ inhibited flg22-induced callose deposition in planta and enhanced disease symptoms caused by attenuated Pseudomonas syringae bacteria. Finally, selected effectors were found to localize to various plant subcellular compartments. These results indicate that X. euvesicatoria bacteria utilize multiple T3S effectors to suppress flg22-induced signaling acting downstream or in parallel to MAP kinase cascades and suggest they act through different molecular mechanisms. PMID:27529660

  1. Tracking the Cognitive, Social, and Neuroanatomical Profile in Early Neurodegeneration: Type III Cockayne Syndrome.

    Science.gov (United States)

    Baez, Sandra; Couto, Blas; Herrera, Eduar; Bocanegra, Yamile; Trujillo-Orrego, Natalia; Madrigal-Zapata, Lucia; Cardona, Juan Felipe; Manes, Facundo; Ibanez, Agustin; Villegas, Andres

    2013-01-01

    Cockayne syndrome (CS) is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration, and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications, and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind, and empathy) tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language, and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions), which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor's brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging.

  2. Tracking the cognitive, social and neuroanatomical profile in early neurodegeneration: Type III Cockayne syndrome

    Directory of Open Access Journals (Sweden)

    Sandra eBaez

    2013-11-01

    Full Text Available Cockayne syndrome (CS is an autosomal recessive disease associated with premature aging, progressive multiorgan degeneration and nervous system abnormalities including cerebral and cerebellar atrophy, brain calcifications and white matter abnormalities. Although several clinical descriptions of CS patients have reported developmental delay and cognitive impairment with relative preservation of social skills, no previous studies have carried out a comprehensive neuropsychological and social cognition assessment. Furthermore, no previous research in individuals with CS has examined the relationship between brain atrophy and performance on neuropsychological and social cognition tests. This study describes the case of an atypical late-onset type III CS patient who exceeds the mean life expectancy of individuals with this pathology. The patient and a group of healthy controls underwent a comprehensive assessment that included multiple neuropsychological and social cognition (emotion recognition, theory of mind and empathy tasks. In addition, we compared the pattern of atrophy in the patient to controls and to its concordance with ERCC8 gene expression in a healthy brain. The results showed memory, language and executive deficits that contrast with the relative preservation of social cognition skills. The cognitive profile of the patient was consistent with his pattern of global cerebral and cerebellar loss of gray matter volume (frontal structures, bilateral cerebellum, basal ganglia, temporal lobe, and occipito-temporal/occipito-parietal regions, which in turn was anatomically consistent with the ERCC8 gene expression level in a healthy donor’s brain. The study of exceptional cases, such as the one described here, is fundamental to elucidating the processes that affect the brain in premature aging diseases, and such studies provide an important source of information for understanding the problems associated with normal and pathological aging.

  3. The Type III Secretion System-Related CPn0809 from Chlamydia pneumoniae.

    Directory of Open Access Journals (Sweden)

    Astrid C Engel

    Full Text Available Chlamydia pneumoniae is an intracellular Gram-negative bacterium that possesses a type III secretion system (T3SS, which enables the pathogen to deliver, in a single step, effector proteins for modulation of host-cell functions into the human host cell cytosol to establish a unique intracellular niche for replication. The translocon proteins located at the top of the T3SS needle filament are essential for its function, as they form pores in the host-cell membrane. Interestingly, unlike other Gram-negative bacteria, C. pneumoniae has two putative translocon operons, named LcrH_1 and LcrH_2. However, little is known about chlamydial translocon proteins. In this study, we analyzed CPn0809, one of the putative hydrophobic translocators encoded by the LcrH_1 operon, and identified an 'SseC-like family' domain characteristic of T3S translocators. Using bright-field and confocal microscopy, we found that CPn0809 is associated with EBs during early and very late phases of a C. pneumoniae infection. Furthermore, CPn0809 forms oligomers, and interacts with the T3SS chaperone LcrH_1, via its N-terminal segment. Moreover, expression of full-length CPn0809 in the heterologous host Escherichia coli causes a grave cytotoxic effect that leads to cell death. Taken together, our data indicate that CPn0809 likely represents one of the translocon proteins of the C. pneumoniae T3SS, and possibly plays a role in the translocation of effector proteins in the early stages of infection.

  4. Alterations in Fibronectin Type III Domain Containing 1 Protein Gene Are Associated with Hypertension.

    Directory of Open Access Journals (Sweden)

    Alan Y Deng

    Full Text Available Multiple quantitative trait loci (QTLs for blood pressure (BP have been detected in rat models of human polygenic hypertension. Great challenges confronting us include molecular identifications of individual QTLs. We first defined the chromosome region harboring C1QTL1 to a segment of 1.9 megabases that carries 9 genes. Among them, we identified the gene encoding the fibronectin type III domain containing 1 protein (Fndc1/activator of G protein signaling 8 (Ags8 to be the strongest candidate for C1QTL1, since numerous non-synonymous mutations are found. Moreover, the 5' Fndc1/Ags8 putative promoter contains numerous mutations that can account for its differential expression in kidneys and the heart, prominent organs in modulating BP, although the Fndc1/Ags8 protein was not detectable in these organs under our experimental conditions. This work has provided the premier evidence that Fndc1/Ags8 is a novel and strongest candidate gene for C1QTL1 without completely excluding other 8 genes in the C1QTL1-residing interval. If proven true by future in vivo function studies such as single-gene Fndc1/Ags8 congenics, transgenesis or targeted-gene modifications, it might represent a part of the BP genetic architecture that operates in the upstream position distant from the end-phase physiology of BP control, since it activates a Gbetagamma component in a signaling pathway. Its functional role could validate the concept that a QTL in itself can influence BP 'indirectly' by regulating other genes downstream in a pathway. The elucidation of the mechanisms initiated by Fndc/Ags8 variations will reveal novel insights into the BP modulation via a regulatory hierarchy.

  5. Fine specificity and cross-reactions of monoclonal antibodies to group B streptococcal capsular polysaccharide type III

    DEFF Research Database (Denmark)

    Pincus, Seth H; Moran, Emily; Maresh, Grace;

    2012-01-01

    ) is considered the dominant "protective" immune mediator. Here we study the fine specificity and potential host reactivity of a panel of well-characterized murine monoclonal Abs against the type III CPS by examining the binding of the Abs to intact and neuraminidase-digested GBS, purified CPS, synthetic...... carbohydrate array technology. The anti-CPS(III) mAbs did not react with cells expressing GD3 and GT3, nor did mAbs specific for the host carbohydrates cross-react with GBS, raising questions about the physiological relevance of this cross-reaction. But in the process of these investigations, we...... serendipitously demonstrated cross-reactions of some anti-CPS(III) mAbs with antigens, likely carbohydrates, found on human leukocytes. These studies suggest caution in the development of a maternal vaccine to prevent infection by this important human pathogen....

  6. Spectrum of AGL mutations in Chinese patients with glycogen storage disease type III: identification of 31 novel mutations.

    Science.gov (United States)

    Lu, Chaoxia; Qiu, Zhengqing; Sun, Miao; Wang, Wei; Wei, Min; Zhang, Xue

    2016-07-01

    Glycogen storage disease type III (GSD III), a rare autosomal recessive disease characterized by hepatomegaly, fasting hypoglycemia, growth retardation, progressive myopathy and cardiomyopathy, is caused by deficiency of the glycogen debranching enzyme (AGL). Direct sequencing of human AGL cDNA and genomic DNA has enabled analysis of the underlying genetic defects responsible for GSD III. To date, the frequent mutations in different areas and populations have been described in Italy, Japan, Faroe Islands and Mediterranean area, whereas little has been performed in Chinese population. Here we report a sequencing-based mutation analysis in 43 Chinese patients with GSD III from 41 families. We identified 51 different mutations, including 15 splice-site (29.4%), 11 small deletions (21.6%), 12 nonsense (23.5%), 7 missense (13.7%), 5 duplication (9.8%) and 1 complex deletion/insertion (2.0%), 31 of which are novel mutations. The most common mutation is c.1735+1G>T (11.5%). The association of AGL missense and small in-frame deletion mutations with normal creatine kinase level was observed. Our study extends the spectrum of AGL mutations and suggests a genotype-phenotype correlation in GSD III. PMID:26984562

  7. Biosynthesis of Dictyostelium Discoideum Differentation-Inducing Factor by a Hybrid Type I Fatty Acid A-Type III polyketide synthase

    Energy Technology Data Exchange (ETDEWEB)

    Austin,M.; Saito, T.; Bowman, M.; Haydock, S.; Kato, A.; Moore, B.; Kay, R.; Noel, J.

    2006-01-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two {approx}3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis.

  8. Purification, crystal structure determination and functional characterization of type III antifreeze proteins from the European eelpout Zoarces viviparus

    DEFF Research Database (Denmark)

    Wilkens, Casper; Poulsen, Jens-Christian Navarro; Ramløv, Hans;

    2014-01-01

    Antifreeze proteins (AFPs) are essential components of many organisms adaptation to cold temperatures. Fish type III AFPs are divided into two groups, SP isoforms being much less active than QAE1 isoforms. Two type III AFPs from Zoarces viviparus, a QAE1 (ZvAFP13) and an SP (ZvAFP6) isoform...

  9. Bioinformatics-enabled identification of the HrpL regulon and type III secretion system effector proteins of Pseudomonas syringae pv. phaseolicola 1448A

    Science.gov (United States)

    The ability of Pseudomonas syringae pv. phaseolicola to cause halo blight of bean is dependent on its ability to translocate effector proteins into host cells via the Hrp type III secretion system (T3SS). To identity genes encoding type III effectors and other potential virulence factors that are r...

  10. Inheritance of Pantoea type III secretion systems through both vertical and horizontal transfer.

    Science.gov (United States)

    Kirzinger, Morgan W B; Butz, Cory J; Stavrinides, John

    2015-12-01

    The type III secretion system (T3SS) is an extracellular apparatus used by many Gram-negative bacteria to deliver effector proteins directly into plant and animal cells, thereby facilitating host-specific association. Strains of the enterobacterial genus, Pantoea, have been isolated from a wide variety of hosts, including plants, insects, and humans, yet it is unclear whether the T3SS may be involved in these associations. In this study, we use comparative genomics and phylogenetic methods to examine the origin and distribution of T3SSs in 35 sequenced environmental and clinical strains of Pantoea. We began our analysis by examining the distribution of the previously characterized plant cell-specific PSI-1 and animal cell-specific PSI-2 of the plant pathogenic Pantoea stewartii subsp. stewartii DC283 (PstDC283), and showed that both had a somewhat limited distribution. Our analysis, however, identified two variants of a unique plant cell-specific T3SS (PSI-1a and PSI-1b) in six Pantoea strains, including a clinical isolate. Our genome analysis of PstDC283 also identified a third T3SS that we named PSI-3, which has a similar genetic content and organization to the Salmonella, animal cell-specific SPI-2 system. Phylogenetic analysis of all three systems suggests that the PSI-1 system has been inherited vertically, whereas the newly identified PSI-1a and PSI-1b systems have been acquired independently from other genera within the Enterobacteriaceae. PSI-2 appears to have been acquired horizontally as far back as the Erwinia/Pantoea common ancestor, with evidence of more recent horizontal acquisition of the PSI-3 system. Our results suggest that Pantoea is a relatively old plant pathogen that has lost and subsequently regained different plant-associated T3SSs. This work has broad implications for understanding the host-associating capacity of Pantoea strains, and reveals the propensity for Pantoea isolates to exchange pathogenicity determinants with human

  11. Direct and Indirect Targeting of PP2A by Conserved Bacterial Type-III Effector Proteins.

    Science.gov (United States)

    Jin, Lin; Ham, Jong Hyun; Hage, Rosemary; Zhao, Wanying; Soto-Hernández, Jaricelis; Lee, Sang Yeol; Paek, Seung-Mann; Kim, Min Gab; Boone, Charles; Coplin, David L; Mackey, David

    2016-05-01

    Bacterial AvrE-family Type-III effector proteins (T3Es) contribute significantly to the virulence of plant-pathogenic species of Pseudomonas, Pantoea, Ralstonia, Erwinia, Dickeya and Pectobacterium, with hosts ranging from monocots to dicots. However, the mode of action of AvrE-family T3Es remains enigmatic, due in large part to their toxicity when expressed in plant or yeast cells. To search for targets of WtsE, an AvrE-family T3E from the maize pathogen Pantoea stewartii subsp. stewartii, we employed a yeast-two-hybrid screen with non-lethal fragments of WtsE and a synthetic genetic array with full-length WtsE. Together these screens indicate that WtsE targets maize protein phosphatase 2A (PP2A) heterotrimeric enzyme complexes via direct interaction with B' regulatory subunits. AvrE1, another AvrE-family T3E from Pseudomonas syringae pv. tomato strain DC3000 (Pto DC3000), associates with specific PP2A B' subunit proteins from its susceptible host Arabidopsis that are homologous to the maize B' subunits shown to interact with WtsE. Additionally, AvrE1 was observed to associate with the WtsE-interacting maize proteins, indicating that PP2A B' subunits are likely conserved targets of AvrE-family T3Es. Notably, the ability of AvrE1 to promote bacterial growth and/or suppress callose deposition was compromised in Arabidopsis plants with mutations of PP2A genes. Also, chemical inhibition of PP2A activity blocked the virulence activity of both WtsE and AvrE1 in planta. The function of HopM1, a Pto DC3000 T3E that is functionally redundant to AvrE1, was also impaired in specific PP2A mutant lines, although no direct interaction with B' subunits was observed. These results indicate that sub-component specific PP2A complexes are targeted by bacterial T3Es, including direct targeting by members of the widely conserved AvrE-family. PMID:27191168

  12. Inheritance of Pantoea type III secretion systems through both vertical and horizontal transfer.

    Science.gov (United States)

    Kirzinger, Morgan W B; Butz, Cory J; Stavrinides, John

    2015-12-01

    The type III secretion system (T3SS) is an extracellular apparatus used by many Gram-negative bacteria to deliver effector proteins directly into plant and animal cells, thereby facilitating host-specific association. Strains of the enterobacterial genus, Pantoea, have been isolated from a wide variety of hosts, including plants, insects, and humans, yet it is unclear whether the T3SS may be involved in these associations. In this study, we use comparative genomics and phylogenetic methods to examine the origin and distribution of T3SSs in 35 sequenced environmental and clinical strains of Pantoea. We began our analysis by examining the distribution of the previously characterized plant cell-specific PSI-1 and animal cell-specific PSI-2 of the plant pathogenic Pantoea stewartii subsp. stewartii DC283 (PstDC283), and showed that both had a somewhat limited distribution. Our analysis, however, identified two variants of a unique plant cell-specific T3SS (PSI-1a and PSI-1b) in six Pantoea strains, including a clinical isolate. Our genome analysis of PstDC283 also identified a third T3SS that we named PSI-3, which has a similar genetic content and organization to the Salmonella, animal cell-specific SPI-2 system. Phylogenetic analysis of all three systems suggests that the PSI-1 system has been inherited vertically, whereas the newly identified PSI-1a and PSI-1b systems have been acquired independently from other genera within the Enterobacteriaceae. PSI-2 appears to have been acquired horizontally as far back as the Erwinia/Pantoea common ancestor, with evidence of more recent horizontal acquisition of the PSI-3 system. Our results suggest that Pantoea is a relatively old plant pathogen that has lost and subsequently regained different plant-associated T3SSs. This work has broad implications for understanding the host-associating capacity of Pantoea strains, and reveals the propensity for Pantoea isolates to exchange pathogenicity determinants with human

  13. Evidence for alternative quaternary structure in a bacterial Type III secretion system chaperone

    Energy Technology Data Exchange (ETDEWEB)

    Barta, Michael L.; Zhang, Lingling; Picking, Wendy L.; Geisbrecht, Brian V. (UMKC); (OKLU)

    2010-10-05

    Type III secretion systems are a common virulence mechanism in many Gram-negative bacterial pathogens. These systems use a nanomachine resembling a molecular needle and syringe to provide an energized conduit for the translocation of effector proteins from the bacterial cytoplasm to the host cell cytoplasm for the benefit of the pathogen. Prior to translocation specialized chaperones maintain proper effector protein conformation. The class II chaperone, Invasion plasmid gene (Ipg) C, stabilizes two pore forming translocator proteins. IpgC exists as a functional dimer to facilitate the mutually exclusive binding of both translocators. In this study, we present the 3.3 {angstrom} crystal structure of an amino-terminally truncated form (residues 10-155, denoted IpgC10-155) of the class II chaperone IpgC from Shigella flexneri. Our structure demonstrates an alternative quaternary arrangement to that previously described for a carboxy-terminally truncated variant of IpgC (IpgC{sup 1-151}). Specifically, we observe a rotationally-symmetric 'head-to-head' dimerization interface that is far more similar to that previously described for SycD from Yersinia enterocolitica than to IpgC1-151. The IpgC structure presented here displays major differences in the amino terminal region, where extended coil-like structures are seen, as opposed to the short, ordered alpha helices and asymmetric dimerization interface seen within IpgC{sup 1-151}. Despite these differences, however, both modes of dimerization support chaperone activity, as judged by a copurification assay with a recombinant form of the translocator protein, IpaB. Conclusions: From primary to quaternary structure, these results presented here suggest that a symmetric dimerization interface is conserved across bacterial class II chaperones. In light of previous data which have described the structure and function of asymmetric dimerization, our results raise the possibility that class II chaperones may

  14. Direct and Indirect Targeting of PP2A by Conserved Bacterial Type-III Effector Proteins.

    Directory of Open Access Journals (Sweden)

    Lin Jin

    2016-05-01

    Full Text Available Bacterial AvrE-family Type-III effector proteins (T3Es contribute significantly to the virulence of plant-pathogenic species of Pseudomonas, Pantoea, Ralstonia, Erwinia, Dickeya and Pectobacterium, with hosts ranging from monocots to dicots. However, the mode of action of AvrE-family T3Es remains enigmatic, due in large part to their toxicity when expressed in plant or yeast cells. To search for targets of WtsE, an AvrE-family T3E from the maize pathogen Pantoea stewartii subsp. stewartii, we employed a yeast-two-hybrid screen with non-lethal fragments of WtsE and a synthetic genetic array with full-length WtsE. Together these screens indicate that WtsE targets maize protein phosphatase 2A (PP2A heterotrimeric enzyme complexes via direct interaction with B' regulatory subunits. AvrE1, another AvrE-family T3E from Pseudomonas syringae pv. tomato strain DC3000 (Pto DC3000, associates with specific PP2A B' subunit proteins from its susceptible host Arabidopsis that are homologous to the maize B' subunits shown to interact with WtsE. Additionally, AvrE1 was observed to associate with the WtsE-interacting maize proteins, indicating that PP2A B' subunits are likely conserved targets of AvrE-family T3Es. Notably, the ability of AvrE1 to promote bacterial growth and/or suppress callose deposition was compromised in Arabidopsis plants with mutations of PP2A genes. Also, chemical inhibition of PP2A activity blocked the virulence activity of both WtsE and AvrE1 in planta. The function of HopM1, a Pto DC3000 T3E that is functionally redundant to AvrE1, was also impaired in specific PP2A mutant lines, although no direct interaction with B' subunits was observed. These results indicate that sub-component specific PP2A complexes are targeted by bacterial T3Es, including direct targeting by members of the widely conserved AvrE-family.

  15. Ethylene polymerization by PN3-type pincer chromium(III) complexes

    KAUST Repository

    Gong, Dirong

    2014-12-01

    Chromium (III) complexes, Cr1, [2,6-(tBu2PNH) 2C5H4N]CrCl3; Cr2, [2,6-(Ph 2PNH)2C5H4N]CrCl3; Cr3, [2-(tBu2PNH)C5H4N]CrCl3 THF; Cr4, [6-(tBu2PNH)C5H4N-2- CH2NEt2]CrCl3; Cr5, [6-(tBu 2PNH)C5H4N-2-C3H2N 2]CrCl3; Cr6, [6-(tBu2PNH)C 5H4N-2-(3,5-Me2)C3H 2N2]CrCl3; Cr7, [6-(tBu 2PNH)C5H4N-2-(3,5-iPr 2)C3H2N2]CrCl3; Cr8, [6-(tBu2PNH)C5H4N-2-(3,5-Ph 2)C3H2N2]CrCl3, bearing a family of neutral PN3-type pincer ligands have been prepared. The molecular structure of Cr2 was further elucidated by the X-ray crystallographic analysis, showing an octahedral geometry. Treatment of these complexes with MAO or alkylaluminum led to catalysts with moderate activities (about 105 g (PE)/Cr(mol) h) for ethylene polymerization, affording exclusively linear low molecular weight solid PE without any detectable oligomers. Among Cr1-Cr8, the highest activity was achieved for Cr1/MAO at room temperature with production of PE with highest molecular weight, indicating that replacement of both tBu groups in Cr1 with Ph groups, or one PtBu2 with the N (imine) arm, resulted in a lower catalytic activity and lower M w. © 2014 Elsevier B.V.

  16. Crystallization and preliminary crystallographic analysis of an acridone-producing novel multifunctional type III polyketide synthase from Huperzia serrata

    International Nuclear Information System (INIS)

    An acridone-producing novel type III polyketide synthase from H. serrata has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 2.0 Å. Polyketide synthase 1 (PKS1) from Huperzia serrata is a plant-specific type III polyketide synthase that shows an unusually versatile catalytic potential, producing various aromatic tetraketides, including chalcones, benzophenones, phlorogulucinols and acridones. Recombinant H. serrata PKS1 expressed in Escherichia coli was crystallized using the hanging-drop vapour-diffusion method. The crystals belonged to space group I222 or I212121, with unit-cell parameters a = 73.3, b = 85.0, c = 137.7 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.0 Å resolution using synchrotron radiation at BL24XU of SPring-8

  17. The Dynamics of an Impulsive Predator-Prey System with Stage Structure and Holling Type III Functional Response

    Directory of Open Access Journals (Sweden)

    Zhixiang Ju

    2015-01-01

    Full Text Available Based on the biological resource management of natural resources, a stage-structured predator-prey model with Holling type III functional response, birth pulse, and impulsive harvesting at different moments is proposed in this paper. By applying comparison theorem and some analysis techniques, the global attractivity of predator-extinction periodic solution and the permanence of this system are studied. At last, examples and numerical simulations are given to verify the validity of the main results.

  18. The Bacterium Pantoea stewartii Uses Two Different Type III Secretion Systems To Colonize Its Plant Host and Insect Vector

    OpenAIRE

    Correa, Valdir R.; Majerczak, Doris R.; Ammar, El-Desouky; Merighi, Massimo; Pratt, Richard C.; Saskia A Hogenhout; Coplin, David L.; Redinbaugh, Margaret G.

    2012-01-01

    Plant- and animal-pathogenic bacteria utilize phylogenetically distinct type III secretion systems (T3SS) that produce needle-like injectisomes or pili for the delivery of effector proteins into host cells. Pantoea stewartii subsp. stewartii (herein referred to as P. stewartii), the causative agent of Stewart's bacterial wilt and leaf blight of maize, carries phylogenetically distinct T3SSs. In addition to an Hrc-Hrp T3SS, known to be essential for maize pathogenesis, P. stewartii has a secon...

  19. Comparison of backbone dynamics of the type III antifreeze protein and antifreeze-like domain of human sialic acid synthase

    International Nuclear Information System (INIS)

    Antifreeze proteins (AFPs) are found in a variety of cold-adapted (psychrophilic) organisms to promote survival at subzero temperatures by binding to ice crystals and decreasing the freezing temperature of body fluids. The type III AFPs are small globular proteins that consist of one α-helix, three 310-helices, and two β-strands. Sialic acids play important roles in a variety of biological functions, such as development, recognition, and cell adhesion and are synthesized by conserved enzymatic pathways that include sialic acid synthase (SAS). SAS consists of an N-terminal catalytic domain and a C-terminal antifreeze-like (AFL) domain, which is similar to the type III AFPs. Despite having very similar structures, AFL and the type III AFPs exhibit very different temperature-dependent stability and activity. In this study, we have performed backbone dynamics analyses of a type III AFP (HPLC12 isoform) and the AFL domain of human SAS (hAFL) at various temperatures. We also characterized the structural/dynamic properties of the ice-binding surfaces by analyzing the temperature gradient of the amide proton chemical shift and its correlation with chemical shift deviation from random coil. The dynamic properties of the two proteins were very different from each other. While HPLC12 was mostly rigid with a few residues exhibiting slow motions, hAFL showed fast internal motions at low temperature. Our results provide insight into the molecular basis of thermostability and structural flexibility in homologous psychrophilic HPLC12 and mesophilic hAFL proteins

  20. Comparison of backbone dynamics of the type III antifreeze protein and antifreeze-like domain of human sialic acid synthase

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yong-Geun [Gyeongsang National University, Department of Chemistry and Research Institute of Natural Science (Korea, Republic of); Park, Chin-Ju [Gwangju Institute of Science and Technology, Division of Liberal Arts and Sciences and Department of Chemistry (Korea, Republic of); Kim, Hee-Eun; Seo, Yeo-Jin; Lee, Ae-Ree; Choi, Seo-Ree; Lee, Shim Sung; Lee, Joon-Hwa, E-mail: joonhwa@gnu.ac.kr [Gyeongsang National University, Department of Chemistry and Research Institute of Natural Science (Korea, Republic of)

    2015-02-15

    Antifreeze proteins (AFPs) are found in a variety of cold-adapted (psychrophilic) organisms to promote survival at subzero temperatures by binding to ice crystals and decreasing the freezing temperature of body fluids. The type III AFPs are small globular proteins that consist of one α-helix, three 3{sub 10}-helices, and two β-strands. Sialic acids play important roles in a variety of biological functions, such as development, recognition, and cell adhesion and are synthesized by conserved enzymatic pathways that include sialic acid synthase (SAS). SAS consists of an N-terminal catalytic domain and a C-terminal antifreeze-like (AFL) domain, which is similar to the type III AFPs. Despite having very similar structures, AFL and the type III AFPs exhibit very different temperature-dependent stability and activity. In this study, we have performed backbone dynamics analyses of a type III AFP (HPLC12 isoform) and the AFL domain of human SAS (hAFL) at various temperatures. We also characterized the structural/dynamic properties of the ice-binding surfaces by analyzing the temperature gradient of the amide proton chemical shift and its correlation with chemical shift deviation from random coil. The dynamic properties of the two proteins were very different from each other. While HPLC12 was mostly rigid with a few residues exhibiting slow motions, hAFL showed fast internal motions at low temperature. Our results provide insight into the molecular basis of thermostability and structural flexibility in homologous psychrophilic HPLC12 and mesophilic hAFL proteins.

  1. Determination of the Stoichiometry of the Complete Bacterial Type III Secretion Needle Complex Using a Combined Quantitative Proteomic Approach.

    Science.gov (United States)

    Zilkenat, Susann; Franz-Wachtel, Mirita; Stierhof, York-Dieter; Galán, Jorge E; Macek, Boris; Wagner, Samuel

    2016-05-01

    Precisely knowing the stoichiometry of their components is critical for investigating structure, assembly, and function of macromolecular machines. This has remained a technical challenge in particular for large, hydrophobic membrane-spanning protein complexes. Here, we determined the stoichiometry of a type III secretion system of Salmonella enterica serovar Typhimurium using two complementary protocols of gentle complex purification combined with peptide concatenated standard and synthetic stable isotope-labeled peptide-based mass spectrometry. Bacterial type III secretion systems are cell envelope-spanning effector protein-delivery machines essential for colonization and survival of many Gram-negative pathogens and symbionts. The membrane-embedded core unit of these secretion systems, termed the needle complex, is composed of a base that anchors the machinery to the inner and outer membranes, a hollow filament formed by inner rod and needle subunits that serves as conduit for substrate proteins, and a membrane-embedded export apparatus facilitating substrate translocation. Structural analyses have revealed the stoichiometry of the components of the base, but the stoichiometry of the essential hydrophobic export apparatus components and of the inner rod protein remain unknown. Here, we provide evidence that the export apparatus of type III secretion systems contains five SpaP, one SpaQ, one SpaR, and one SpaS. We confirmed that the previously suggested stoichiometry of nine InvA is valid for assembled needle complexes and describe a loose association of InvA with other needle complex components that may reflect its function. Furthermore, we present evidence that not more than six PrgJ form the inner rod of the needle complex. Providing this structural information will facilitate efforts to obtain an atomic view of type III secretion systems and foster our understanding of the function of these and related flagellar machines. Given that other virulence

  2. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

    DEFF Research Database (Denmark)

    Veidal, Sanne S; Vassiliadis, Efstathios; Barascuk, Natasha;

    2010-01-01

    During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via their...... activity in the proteolytic degradation of extracellular macromolecules such as collagens, resulting in the generation of specific cleavage fragments. These neo-epitopes may be used as markers of fibrosis....

  3. Use of amino terminal type III procollagen peptide (P3NP) assay in methotrexate therapy for psoriasis

    OpenAIRE

    Khan, S; Subedi, D; Chowdhury, M M U

    2006-01-01

    Hepatic fibrosis continues to be a risk in patients receiving methotrexate for psoriasis. Measurement of amino terminal levels of type III procollagen (P3NP) has been advocated as an effective non‐invasive test for ongoing hepatic fibrogenesis that could avoid liver biopsies. An audit was conducted to assess the practice of P3NP monitoring using guidelines produced by Manchester and whether the agreed levels correlate with histological severity. Sixty five patients with 174 P3NP assays and 30...

  4. Engineered biosynthesis of plant polyketides: chain length control in an octaketide-producing plant type III polyketide synthase.

    Science.gov (United States)

    Abe, Ikuro; Oguro, Satoshi; Utsumi, Yoriko; Sano, Yukie; Noguchi, Hiroshi

    2005-09-14

    The chalcone synthase (CHS) superfamily of type III polyketide synthases (PKSs) produces a variety of plant secondary metabolites with remarkable structural diversity and biological activities (e.g., chalcones, stilbenes, benzophenones, acrydones, phloroglucinols, resorcinols, pyrones, and chromones). Here we describe an octaketide-producing novel plant-specific type III PKS from aloe (Aloe arborescens) sharing 50-60% amino acid sequence identity with other plant CHS-superfamily enzymes. A recombinant enzyme expressed in Escherichia coli catalyzed seven successive decarboxylative condensations of malonyl-CoA to yield aromatic octaketides SEK4 and SEK4b, the longest polyketides known to be synthesized by the structurally simple type III PKS. Surprisingly, site-directed mutagenesis revealed that a single residue Gly207 (corresponding to the CHS's active site Thr197) determines the polyketide chain length and product specificity. Small-to-large substitutions (G207A, G207T, G207M, G207L, G207F, and G207W) resulted in loss of the octaketide-forming activity and concomitant formation of shorter chain length polyketides (from triketide to heptaketide) including a pentaketide chromone, 2,7-dihydroxy-5-methylchromone, and a hexaketide pyrone, 6-(2,4-dihydroxy-6-methylphenyl)-4-hydroxy-2-pyrone, depending on the size of the side chain. Notably, the functional diversity of the type III PKS was shown to evolve from simple steric modulation of the chemically inert single residue lining the active-site cavity accompanied by conservation of the Cys-His-Asn catalytic triad. This provided novel strategies for the engineered biosynthesis of pharmaceutically important plant polyketides. PMID:16144421

  5. DYNC2H1 Mutations Cause Asphyxiating Thoracic Dystrophy and Short Rib-Polydactyly Syndrome, Type III

    OpenAIRE

    Dagoneau, Nathalie; Goulet, Marie; Geneviève, David; Sznajer, Yves; Martinovic, Jelena; Smithson, Sarah; Huber, Céline; Baujat, Geneviève; Flori, Elisabeth; Tecco, Laura; Cavalcanti, Denise; Delezoide, Anne-Lise; Serre, Valérie; Le Merrer, Martine; Munnich, Arnold

    2009-01-01

    Jeune asphyxiating thoracic dystrophy (ATD) is an autosomal-recessive chondrodysplasia characterized by short ribs and a narrow thorax, short long bones, inconstant polydactyly, and trident acetabular roof. ATD is closely related to the short rib polydactyly syndrome (SRP) type III, which is a more severe condition characterized by early prenatal expression and lethality and variable malformations. We first excluded IFT80 in a series of 26 fetuses and children belonging to 14 families diagnos...

  6. Diagnosing the Source Region of a Solar Burst on 26 September 2011 by Microwave Type III Pairs

    CERN Document Server

    Tan, Baolin; Meszarosova, Hana; Kashapova, Larisa; Huang, Jing; Yan, Yan; Kontar, Eduard P

    2016-01-01

    This work reports a peculiar and interesting train of microwave type III pair bursts in the impulsive rising phase of a solar flare on 2011 September 26. The observations include radio spectrometers at frequency of 0.80 - 2.00 GHz, hard X-ray (RHESSI and FERMI), EUV images of SWAP/PROBA-2 and magnetogram of HMI/SDO. By using a recently developed method (Tan et al. 2016a), we diagnosed the plasma density, temperature, plasma beta, magnetic field near the source region, the energy of energetic electrons and the distance between the acceleration region and the emission start sites of type III bursts. From the diagnostics, we find that: (1) The plasma density, temperature, magnetic field, and the distance between the acceleration region and the emission start sites almost have no obvious variations during the period of type III pair trains, while the energy of electrons has an obvious peak value which is consistent to the hard X-ray emission. (2) The plasma beta is much higher than an unity showing a highly dynam...

  7. Phase Coupling in Langmuir Wave Packets: Evidence for Four Wave Interactions in Solar Type III Radio Bursts

    Science.gov (United States)

    Thejappa, G.; MacDowall, R. J.; Bergamo, M.

    2012-01-01

    The four wave interaction process, known as the oscillating two stream instability (OTSI) is considered as one of the mechanisms responsible for stabilizing the electron beams associated with solar type III radio bursts. It has been reported that (1) an intense localized Langmuir wave packet associated with a type III burst contains the spectral characteristics of the OTSI: (a) a resonant peak at the local electron plasma frequency, f(sub pe), (b) a Stokes peak at a frequency slightly lower than f(sub pe), (c) anti-Stokes peak at a frequency slightly higher than f(sub pe), and (d) a low frequency enhancement below a few hundred Hz, (2) the frequencies and wave numbers of these spectral components satisfy the resonance conditions of the OTSI, and (3) the peak intensity of the wave packet is well above the thresholds for the OTSI as well as spatial collapse of envelope solitons. Here, for the first time, applying the trispectral analysis on this wave packet, we show that the tricoherence, which measures the degree of coherent four-wave coupling amongst the observed spectral components exhibits a peak. This provides an additional evidence for the OTSI and related spatial collapse of Langmuir envelope solitons in type III burst sources.

  8. Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases.

    Science.gov (United States)

    Loundras, Eleni-Anna; Herod, Morgan R; Harris, Mark; Stonehouse, Nicola J

    2016-09-01

    Foot-and-mouth disease virus (FMDV) causes economically damaging infections of cloven-hooved animals, with outbreaks resulting in large financial losses to the agricultural industry. Due to the highly contagious nature of FMDV, research with infectious virus is restricted to a limited number of key facilities worldwide. FMDV sub-genomic replicons are therefore important tools for the study of viral translation and genome replication. The type III phosphatidylinositol-4-kinases (PI4Ks) are a family of enzymes that plays a key role in the production of replication complexes (viral factories) of a number of positive-sense RNA viruses and represents a potential target for novel pan-viral therapeutics. Here, we investigated whether type III PI4Ks also play a role in the FMDV life cycle, using a combination of FMDV sub-genomic replicons and bicistronic internal ribosome entry site (IRES)-containing reporter plasmids. We demonstrated that replication of the FMDV replicon was unaffected by inhibitors of either PI4KIIIα or PI4KIIIβ. However, PIK93, an inhibitor previously demonstrated to target PI4KIIIβ, did inhibit IRES-mediated protein translation. Consistent with this, cells transfected with FMDV replicons did not exhibit elevated levels of phosphatidylinositol-4-phosphate lipids. These results are therefore supportive of the hypothesis that FMDV genome replication does not require type III PI4K activity and does not activate these kinases. PMID:27323707

  9. Chlamydial Protease-Like Activity Factor and Type III Secreted Effectors Cooperate in Inhibition of p65 Nuclear Translocation

    Science.gov (United States)

    Patton, Michael John; McCorrister, Stuart; Grant, Chris; Westmacott, Garrett; Fariss, Robert; Hu, Pingzhao; Zhao, Kaiqiong; Blake, Mary; Whitmire, Bill; Yang, Chunfu

    2016-01-01

    ABSTRACT The chlamydial protease-like activity factor (CPAF) is hypothesized to be an important secreted virulence factor; however, challenges in denaturing its proteolytic activity have hampered attempts to identify its legitimate targets. Here, we use a genetic and proteomic approach to identify authentic CPAF targets. Human epithelial cells infected with CPAF-sufficient and CPAF-deficient chlamydiae were lysed using known CPAF-denaturing conditions. Their protein profiles were analyzed using isobaric mass tags and liquid chromatography-tandem mass spectrometry. Comparative analysis of CPAF-sufficient and CPAF-deficient infections identified a limited number of CPAF host and chlamydial protein targets. Host targets were primarily interferon-stimulated gene products, whereas chlamydial targets were type III secreted proteins. We provide evidence supporting a cooperative role for CPAF and type III secreted effectors in blocking NF-κB p65 nuclear translocation, resulting in decreased beta interferon and proinflammatory cytokine synthesis. Genetic complementation of null organisms with CPAF restored p65 nuclear translocation inhibition and proteolysis of chlamydial type III secreted effector proteins (T3SEs). We propose that CPAF and T3SEs cooperate in the inhibition of host innate immunity. PMID:27677792

  10. Open reading frame 2 of porcine circovirus type 2 encodes a major capsid protein.

    Science.gov (United States)

    Nawagitgul, P; Morozov, I; Bolin, S R; Harms, P A; Sorden, S D; Paul, P S

    2000-09-01

    Porcine circovirus 2 (PCV2), a single-stranded DNA virus associated with post-weaning multisystemic wasting syndrome of swine, has two potential open reading frames, ORF1 and ORF2, greater than 600 nucleotides in length. ORF1 is predicted to encode a replication-associated protein (Rep) essential for replication of viral DNA, while ORF2 contains a conserved basic amino acid sequence at the N terminus resembling that of the major structural protein of chicken anaemia virus. Thus far, the structural protein(s) of PCV2 have not been identified. In this study, a viral structural protein of 30 kDa was identified in purified PCV2 particles. ORF2 of PCV2 was cloned into a baculovirus expression vector and the gene product was expressed in insect cells. The expressed ORF2 gene product had a molecular mass of 30 kDa, similar to that detected in purified virus particles. The recombinant ORF2 protein self-assembled to form capsid-like particles when viewed by electron microscopy. Antibodies against the ORF2 protein were detected in samples of sera obtained from pigs as early as 3 weeks after experimental infection with PCV2. These results show that the major structural protein of PCV2 is encoded by ORF2 and has a molecular mass of 30 kDa. PMID:10950986

  11. Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development.

    Directory of Open Access Journals (Sweden)

    Shigeto Yoshida

    2007-12-01

    Full Text Available The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50 of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions.

  12. Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development.

    Science.gov (United States)

    Yoshida, Shigeto; Shimada, Yohei; Kondoh, Daisuke; Kouzuma, Yoshiaki; Ghosh, Anil K; Jacobs-Lorena, Marcelo; Sinden, Robert E

    2007-12-01

    The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50) of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions. PMID:18159942

  13. Progressive non-infectious anterior vertebral fusion in a baby with Saethre-Chotzen-acrocephalosyndactyly type III syndrome

    Directory of Open Access Journals (Sweden)

    Али Аль-Каисси

    2015-09-01

    Full Text Available We report on a 3-months old baby of Austrian origin and product of non-consanguineous parents. Abnormal craniofacial contour was the main deformity. The overall clinico-radiographic features were consistent with Saether-Chotzen-acrocephalosyndactyly type III syndrome. Bi-directional sequencing of the exon 8 and of the FGFR3-genes, exons 7 of FGFR3 (Fibroblast growth factor receptor3 genes, the exon 5 of the FGFR1 gene, revealed no mutations. Sagittal MRI imaging of the spine showed anterior vertebral fusion along the thoraco-lumbar vertebrae compatible with the non-infectious type.

  14. Endoscopic treatment of choledochal cyst type III Tratamento endoscópico de cisto de colédoco do tipo III

    Directory of Open Access Journals (Sweden)

    Matheus Alessi Rodrigues

    2008-09-01

    Full Text Available BACKGROUND: Todani type III cysts are not very common disease. Endoscopically the choledochocele is not a challenging diagnosis. Sometimes biliary stone disease is associated and events of cholangitis and pancreatitis may occur. Normally these patients are referred for surgical treatment, mainly because there is a widespread concept that choledocal cysts are very prone to develop neoplasia and must be resected. Nevertheless surgical resection is not free of morbidity. The chance for neoplasia in such cases seems to be related to the presence of pancreaticobiliary reflux towards the common bile duct. AIM: To report a case of endoscopic treatment of choledochal cyst type III with literature review. CASE REPORT: Young man with recurrent abdominal pain, fever and hyperamylasemia. An ERCP showed pancreaticobiliary maljunction and calculus impaction. Papillotomy was performed and complete biliary clearance was achieved. Amylase contents in the common bile duct was measured and normal. Due to absence of pancreatiobiliary reflux, a second endoscopic approach was performed and a wide communication between choledochocele and duodenum was done with diathermy (using the papillotome. The patient recovering was uneventful and in 30 months follow-up he remains asymptomatic. CONCLUSION: Since pancreatobiliary reflux is not present, surgical approach of the diverticulum seemed to be not necessary. Endoscopic drainage of choledococele was a good option for conservative treatment.INTRODUÇÃO: Cisto de colédoco do tipo III de Todani não é doença muito comum. Eventualmente pode ocorrer a presença de doença biliar calculosa, que nestes casos estaria associada a eventos de colangite e pancreatite. Normalmente estes pacientes são conduzidos ao tratamento cirúrgico, principalmente porque há conceito difundido de que os cistos de colédoco são muito propensos a desenvolver neoplasia e que a sua presença indicaria ressecção cirúrgica. A chance para

  15. Two-Higgs-doublet type-II and -III models and t → ch at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Arhrib, A. [Universite Abdelmalek Essaadi, Departement de Mathematiques, Faculte des Sciences et Techniques, B. 416, Tangier (Morocco); National Center for Theoretical Sciences, Physics Division, Hsinchu (China); Benbrik, R. [Cadi Ayyad University, LPHEA, Semlalia, Marrakech (Morocco); Faculte Polydisciplinaire de Safi, MSISM Team, Sidi Bouzid, B.P 4162, Safi (Morocco); Chen, Chuan-Hung [National Cheng-Kung University, Department of Physics, Tainan (China); Gomez-Bock, Melina [Universidad de las Americas Puebla, DAFM, Cholula, PUE (Mexico); Semlali, Souad [Cadi Ayyad University, LPHEA, Semlalia, Marrakech (Morocco)

    2016-06-15

    We study the constraints of the generic two-Higgs-doublet model (2HDM) type-III and the impacts of the new Yukawa couplings. For comparisons, we revisit the analysis in the 2HDM type-II. To understand the influence of all involving free parameters and to realize their correlations, we employ a χ-square fitting approach by including theoretical and experimental constraints, such as the S, T, and U oblique parameters, the production of standard model Higgs and its decay to γγ, WW*/ZZ*, τ{sup +}τ{sup -}, etc. The errors of the analysis are taken at 68, 95.5, and 99.7% confidence levels. Due to the new Yukawa couplings being associated with cos(β - α) and sin(β - α), we find that the allowed regions for sin α and tan β in the type-III model can be broader when the dictated parameter χ{sub F} is positive; however, for negative χ{sub F}, the limits are stricter than those in the type-II model. By using the constrained parameters, we find that the deviation from the SM in h → Zγ can be of O(10 %). Additionally, we also study the top-quark flavor-changing processes induced at the tree level in the type-III model and find that when all current experimental data are considered, we get Br(t → c(h, H)) < 10{sup -3} for m{sub h} = 125.36 and m{sub h} = 150 GeV, and Br(t → cA) slightly exceeds 10{sup -3} for m{sub A} = 130 GeV. (orig.)

  16. Possible radio precursors/signatures of the CMEs onset: radio type III bursts and fine structures in the centimeter-metric wavelength region

    International Nuclear Information System (INIS)

    Seventy-one occurrences of coronal mass ejections (CMEs) associated with radio bursts, seemingly associated with type III bursts/fine structures (FSs), in the centimeter-metric frequency range during 2003-2005, were obtained with the spectrometers at the National Astronomical Observatories, Chinese Academy of Sciences (NAOC) and the Culgoora radio spectrometer and are presented. The statistical results of 68 out of 71 events associated with the radio type III bursts or FSs during the initiation or early stages of the CMEs indicate that most CMEs contain the emissions of radio type III bursts/FSs near the time of the CME's onset, in spite of their fast or slow speeds. Therefore, we propose that type III bursts and FSs are possible precursors of the onset of CMEs. We stress that the radio type III bursts/FSs in the centimeter-metric wavelength region and the CME transients possibly occurred in conjunction with the origin of the coronal precursor structures. Thus, the statistical results support the suggestions that type III bursts/FSs are indicators of extra energy input into the corona at the CMEs' onset, and that the type III bursts/FSs are produced primarily due to a coronal instability which eventually triggers the CME process. This may signify that the centimeter-metric radio bursts corresponding to or near the CME's onset are caused by the disturbed corona (possibly including minor magnetic reconnections).

  17. A human β-III-spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding.

    Science.gov (United States)

    Avery, Adam W; Crain, Jonathan; Thomas, David D; Hays, Thomas S

    2016-01-01

    Spinocerebellar ataxia type 5 (SCA5) is a human neurodegenerative disease that stems from mutations in the SPTBN2 gene encoding the protein β-III-spectrin. Here we investigated the molecular consequence of a SCA5 missense mutation that results in a L253P substitution in the actin-binding domain (ABD) of β-III-spectrin. We report that the L253P substitution in the isolated β-III-spectrin ABD causes strikingly high F-actin binding affinity (Kd = 75.5 nM) compared to the weak F-actin binding affinity of the wild-type ABD (Kd = 75.8 μM). The mutation also causes decreased thermal stability (Tm = 44.6 °C vs 59.5 °C). Structural analyses indicate that leucine 253 is in a loop at the interface of the tandem calponin homology (CH) domains comprising the ABD. Leucine 253 is predicted to form hydrophobic contacts that bridge the CH domains. The decreased stability of the mutant indicates that these bridging interactions are probably disrupted, suggesting that the high F-actin binding affinity of the mutant is due to opening of the CH domain interface. These results support a fundamental role for leucine 253 in regulating opening of the CH domain interface and binding of the ABD to F-actin. This study indicates that high-affinity actin binding of L253P β-III-spectrin is a likely driver of neurodegeneration. PMID:26883385

  18. Differential expression of type III effector BteA protein due to IS481 insertion in Bordetella pertussis.

    Directory of Open Access Journals (Sweden)

    Hyun-Ja Han

    Full Text Available BACKGROUND: Bordetella pertussis is the primary etiologic agent of the disease pertussis. Universal immunization programs have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especially in adolescents and adults, has increased in several countries despite high vaccination coverage. During the last three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in many countries. A comparative proteomic analysis of the strains was performed to identify protein(s involved in the type shift. METHODOLOGY/PRINCIPAL FINDING: Proteomic analysis identified one differentially expressed protein in the B. pertussis strains: the type III cytotoxic effector protein BteA, which is responsible for host cell death in Bordetella bronchiseptica infections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-type strains. Sequence analysis of the vaccine-type strains revealed an IS481 insertion in the 5' untranslated region of bteA, -136 bp upstream of the bteA start codon. A high level of bteA transcripts from the IS481 promoter was detected in the vaccine-type strains, indicating that the transcript might be an untranslatable form. Furthermore, BteA mutant studies demonstrated that BteA expression in the vaccine-type strains is down-regulated by the IS481 insertion. CONCLUSION/SIGNIFICANCE: The cytotoxic effector BteA protein is expressed at higher levels in B. pertussis nonvaccine-type strains than in vaccine-type strains. This type-dependent expression is due to an insertion of IS481 in B. pertussis clinical strains, suggesting that augmented expression of BteA protein might play a key role in the type shift of B. pertussis.

  19. Analysis of viral protein-2 encoding gene of avian encephalomyelitis virus from field specimens in Central Java region, Indonesia

    Directory of Open Access Journals (Sweden)

    Aris Haryanto

    2016-01-01

    Full Text Available Aim: Avian encephalomyelitis (AE is a viral disease which can infect various types of poultry, especially chicken. In Indonesia, the incidence of AE infection in chicken has been reported since 2009, the AE incidence tends to increase from year to year. The objective of this study was to analyze viral protein 2 (VP-2 encoding gene of AE virus (AEV from various species of birds in field specimen by reverse transcription polymerase chain reaction (RT-PCR amplification using specific nucleotides primer for confirmation of AE diagnosis. Materials and Methods: A total of 13 AEV samples are isolated from various species of poultry which are serologically diagnosed infected by AEV from some areas in central Java, Indonesia. Research stage consists of virus samples collection from field specimens, extraction of AEV RNA, amplification of VP-2 protein encoding gene by RT-PCR, separation of RT-PCR product by agarose gel electrophoresis, DNA sequencing and data analysis. Results: Amplification products of the VP-2 encoding gene of AEV by RT-PCR methods of various types of poultry from field specimens showed a positive results on sample code 499/4/12 which generated DNA fragment in the size of 619 bp. Sensitivity test of RT-PCR amplification showed that the minimum concentration of RNA template is 127.75 ng/μl. The multiple alignments of DNA sequencing product indicated that positive sample with code 499/4/12 has 92% nucleotide homology compared with AEV with accession number AV1775/07 and 85% nucleotide homology with accession number ZCHP2/0912695 from Genbank database. Analysis of VP-2 gene sequence showed that it found 46 nucleotides difference between isolate 499/4/12 compared with accession number AV1775/07 and 93 nucleotides different with accession number ZCHP2/0912695. Conclusions: Analyses of the VP-2 encoding gene of AEV with RT-PCR method from 13 samples from field specimen generated the DNA fragment in the size of 619 bp from one sample with

  20. Training improves oxidative capacity, but not function, in spinal muscular atrophy type III

    DEFF Research Database (Denmark)

    Madsen, Karen Lindhardt; Hansen, Regitze Sølling; Preisler, Nicolai;

    2015-01-01

    a 12-week training program, performing 42 30-minute sessions exercising at 65-70% of maximal oxygen uptake (VO2max ). VO2max , muscle strength, functional tests, and self-reported activities of daily living were assessed before and after the training. RESULTS: Training induced a 27 ± 3% increase in VO2......max (17 ± 2 to 21 ± 2 ml/kg/min, P sleep in 3 patients, and led to training modifications in 2 patients. CONCLUSIONS: Cycle exercise improves VO2max in SMA III without causing muscle...

  1. Kubas-type hydrogen storage in V(III) polymers using tri- and tetradentate bridging ligands.

    Science.gov (United States)

    Hoang, Tuan K A; Hamaed, Ahmad; Moula, Golam; Aroca, Ricardo; Trudeau, Michel; Antonelli, David M

    2011-04-01

    Oxalic acid, oxamide, glycolic acid, and glycolamide were employed as 2-carbon linkers to synthesize a series of one-dimensional V(III) polymers from trismesityl vanadium(III)·THF containing a high concentration of low-valent metal sites that can be exploited for Kubas binding in hydrogen storage. Synthesized materials were characterized by powder X-ray diffraction (PXRD), nitrogen adsorption (BET), X-ray photoelectron spectroscopy (XPS), infrared spectroscopy (IR), Raman spectroscopy, thermogravimetric analysis, and elemental analysis. Because each of these organic linkers possesses a different number of protons and coordinating atoms, the products in each case were expected to have different stoichiometries with respect to the number of mesityl groups eliminated and also a different geometry about the V(III) centers. For example, the oxalate and glycolate polymers contained residual mesityl groups; however, these could be exchanged with hydride via hydrogenolysis. The highest adsorption capacity was recorded on the product of trismesityl vanadium(III)·THF with oxamide (3.49 wt % at 77 K and 85 bar). As suggested by the high enthalpy of adsorption (17.9 kJ/mol H(2)), a substantial degree of performance of the vanadium metal centers was retained at room temperature (25%), corresponding to a gravimetric adsorption of 0.87 wt % at 85 bar, close to the performance of MOF-177 at this temperature and pressure. This is remarkable given the BET surface area of this material is only 9 m(2)/g. A calculation on the basis of thermogravimetric results provides 0.88 hydrogen molecule per vanadium center under these conditions. Raman studies with H(2) and D(2) showed the first unequivocal evidence for Kubas binding on a framework metal in an extended solid, and IR studies demonstrated H(D) exchange of the vanadium hydride with coordinated D(2). These spectroscopic observations are sufficient to assign the rising trends in isosteric heats of hydrogen adsorption observed

  2. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid–type III polyketide synthase

    OpenAIRE

    Austin, Michael B; Saito, Tamao; Bowman, Marianne E.; Haydock, Stephen; Kato, Atsushi; Moore, Bradley S.; Kay, Robert R.; Noel, Joseph P.

    2006-01-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two ~3,000-residue D. discoideum proteins, termed ‘steely’, as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid syntha...

  3. Deep vein thrombosis, an unreported first manifestation of polyglandular autoimmune syndrome type III

    Directory of Open Access Journals (Sweden)

    M Horsey

    2016-07-01

    Full Text Available A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA, confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL, decreased serum B12 levels (56pg/mL, with resultant increased methylmalonic acid (5303nmol/L and hyperhomocysteinemia (131μmol/L, the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD, and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B, defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases.

  4. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems.

    Directory of Open Access Journals (Sweden)

    Ram Samudrala

    2009-04-01

    Full Text Available The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates--effector proteins--are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating protein sequence-based features, including evolutionary measures such as the pattern of homologs in a range of other organisms, G+C content, amino acid composition, and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from the plant pathogen Pseudomonas syringae and validated on a set of effectors from the animal pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium after eliminating effectors with detectable sequence similarity. We show that this approach can predict known secreted effectors with high specificity and sensitivity. Furthermore, by considering a large set of effectors from multiple organisms, we computationally identify a common putative secretion signal in the N-terminal 20 residues of secreted effectors. This signal can be used to discriminate 46 out of 68 total known effectors from both organisms, suggesting that it is a real, shared signal applicable to many type III secreted effectors. We use the method to make novel predictions of secreted effectors in S. Typhimurium, some of which have been experimentally validated. We also apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis, identifying the majority of known secreted proteins in addition to providing a number of novel predictions. This approach provides a new way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  5. Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems

    Energy Technology Data Exchange (ETDEWEB)

    Samudrala, Ram; Heffron, Fred; McDermott, Jason E.

    2009-04-24

    The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates, effector proteins, are not. We have used a machine learning approach to identify new secreted effectors. The method integrates evolutionary measures, such as the pattern of homologs in a range of other organisms, and sequence-based features, such as G+C content, amino acid composition and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from Salmonella typhimurium and validated on a corresponding set of effectors from Pseudomonas syringae, after eliminating effectors with detectable sequence similarity. The method was able to identify all of the known effectors in P. syringae with a specificity of 84% and sensitivity of 82%. The reciprocal validation, training on P. syringae and validating on S. typhimurium, gave similar results with a specificity of 86% when the sensitivity level was 87%. These results show that type III effectors in disparate organisms share common features. We found that maximal performance is attained by including an N-terminal sequence of only 30 residues, which agrees with previous studies indicating that this region contains the secretion signal. We then used the method to define the most important residues in this putative secretion signal. Finally, we present novel predictions of secreted effectors in S. typhimurium, some of which have been experimentally validated, and apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis. This approach is a novel and effective way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.

  6. [Medium-term outcome, follow-up, and quality of life in children treated for type III esophageal atresia].

    Science.gov (United States)

    Lepeytre, C; De Lagausie, P; Merrot, T; Baumstarck, K; Oudyi, M; Dubus, J-C

    2013-10-01

    The aim of this study was to evaluate the medium-term outcome (health status, medical and surgical French National Health Authority-recommended follow-up, and quality of life) of children born with type III esophageal atresia (EA). Previous events (during the perinatal period, associated abnormalities, respiratory and digestive complications) of children treated for type III EA at the Marseille university hospitals between 1999 and 2009 were noted. Parents completed a standardized questionnaire concerning the health of their children during the previous year, and a quality-of-life questionnaire (PedsQL 4.0) was also completed by children aged more than 8 years. Among the 68 children treated, 44 responded to our solicitation (mean age, 7.6 years; range, 3-12.8 years). Previous important events were : pneumonia(s) (65%), asthma before the age of 3 years (66%), hospitalization for a respiratory event (45%), fundoplication (20%), and esophageal dilatation (45%). We noted current chronic cough (16%), asthma (30%), dysphagia (39%), and symptomatic gastroesophageal reflux (9%). National guidelines were not respected, except for the surgical indications in children aged less than 6 years. The quality-of-life scores (n=43 children) were similar to healthy controls but were negatively influenced by a gastrostomy procedure (P=0.020), pneumonia (P=0.013), and hospitalization due to a respiratory event (P=0.006) or a digestive event (P=0.010), and also by current asthma (P=0.004). In conclusion, despite recurrent respiratory or digestive symptoms and inadequate recommended follow-up, the quality of life of children treated for type III of EA is good.

  7. History of settlement of villages from Central Tunisia by studying families sharing a common founder Glycogenosis type III mutation.

    Science.gov (United States)

    Rhouma, Faten Ben; Messai, Habib; Hsouna, Sana; Halim, Nizar Ben; Cherif, Wafa; Fadhel, Sihem Ben; Tiar, Afaf; Nagara, Majdi; Azzouz, Hatem; Sfar, Mohamed-Tahar; Dridi, Marie-Françoise Ben; Tebib, Neji; Ayadi, Abdelkarim; Abdelhak, Sonia; Kefi, Rym

    2016-09-01

    Glycogen storage disease type III (GSD III; Cori disease; Forbes disease) is an autosomal recessive inherited metabolic disorder resulting from deficient glycogen debrancher enzyme activity in liver and muscle. In this study, we focused on a single AGL gene mutation p.W1327X in 16 Tunisian patients from rural area surrounding the region of Mahdia in Central Tunisia. This constitutes the largest pool of patients with this mutation ever described. This study was performed to trace the history of the patients' ancestries in a single region. After extraction of genomic DNA, exon 31 of AGL gene was sequenced. The patients were investigated for the hypervariable segment 1 of mitochondrial DNA and 17 Y-STR markers. We found that the p.W1327X mutation was a founder mutation in Tunisia Analysis of maternal lineages shows an admixture of autochthonous North African, sub-Saharan and a predominance of Eurasian haplogroups. Heterogeneity of maternal haplogroups indicates an ancient settlement. However, paternal gene flow was highly homogeneous and originates from the Near East. We hypothesize that the p.W1327X mutation was introduced into the Tunisian population probably by a recent migration event; then the mutation was fixed in a small region due to the high rate of consanguineous marriages and genetic drift. The screening for this mutation should be performed in priority for GSD III molecular diagnosis, for patients from the region of Mahdia and those from regions sharing the same settlement history. PMID:26704523

  8. Genome sequence of a dissimilatory Fe(III)-reducing bacterium Geobacter soli type strain GSS01(T).

    Science.gov (United States)

    Yang, Guiqin; Chen, Shanshan; Zhou, Shungui; Liu, Yongfeng

    2015-01-01

    Strain GSS01(T) (=KCTC 4545=MCCC 1 K00269) is the type strain of the species Geobacter soli. G. soli strain GSS01(T) is of interest due to its ability to reduce insoluble Fe(III) oxides with a wide range of electron donors. Here we describe some key features of this strain, together with the whole genome sequence and annotation. The genome of size 3,657,100 bp contains 3229 protein-coding and 54 RNA genes, including 2 16S rRNA genes. The genome of strain GSS01(T)contains 76 predicted cytochrome genes, 24 pilus assembly protein genes and several other genes, which were proposed to be related to the reduction of insoluble Fe(III) oxides. The genes associated with the electron donors and acceptors of strain GSS01(T) were predicted in the genome. Information gained from its sequence will be relevant to the future elucidation of extracellular electron transfer mechanism during the reduction of Fe(III) oxides. PMID:26634019

  9. Two-Higgs-Doublet type-II and -III models and $t\\to c h$ at the LHC

    CERN Document Server

    Arhrib, A; Chen, Chuan-Hung; Gomez-Bock, M; Semlali, S

    2015-01-01

    Based on the updated $8$ TeV LHC data for the Higgs searches, we study the constraints of generic two-Higgs-doublet model (2HDM) type-III and the impacts of the new Yukawa couplings. For comparisons, we revisit the analysis in 2HDM type-II. For understanding the influence of all involving free parameters and realizing their correlations, we employ $\\chi$-square fitting approach by including theoretical and experimental constraints, such as $B\\to X_s \\gamma$, $B_q-\\bar B_q$ mixing, S, T and U oblique parameters, the production of standard model Higgs and its decay to $\\gamma\\gamma$, $WW^*/ZZ^*$, $\\tau^+ \\tau^-$, etc. The errors of analysis are taken at $68\\%$, $95.5\\%$ and $99.7\\%$ confidence level. Due to the new Yukawa couplings being associated with $\\cos(\\alpha-\\beta)$ and $\\sin(\\alpha-\\beta)$, we find that the allowed regions for $\\sin\\alpha$ and $\\tan\\beta$ in type-III could be broader when the dictated parameter $\\chi_F$ is positive; however, for negative $\\chi_F$, the limits are more strict than those ...

  10. Crystal structures of type III{sub H} NAD-dependent D-3-phosphoglycerate dehydrogenase from two thermophiles

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S.M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Pampa, K.J. [Department of Studies in Microbiology, University of Mysore, Mysore 570 006 (India); Manjula, M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Hemantha Kumar, G. [Department of Studies in Computer Science, University of Mysore, Mysore 570 006 (India); Kunishima, Naoki [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, Hyogo 679-5148 (Japan); Lokanath, N.K., E-mail: lokanath@physics.uni-mysore.ac.in [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India)

    2014-08-15

    Highlights: • Determined the crystal structures of PGDH from two thermophiles. • Monomer is composed of nucleotide binding domain and substrate binding domain. • Crystal structures of type III{sub H} PGDH. - Abstract: In the L-Serine biosynthesis, D-3-phosphoglycerate dehydrogenase (PGDH) catalyzes the inter-conversion of D-3-phosphoglycerate to phosphohydroxypyruvate. PGDH belongs to 2-hydroxyacid dehydrogenases family. We have determined the crystal structures of PGDH from Sulfolobus tokodaii (StPGDH) and Pyrococcus horikoshii (PhPGDH) using X-ray diffraction to resolution of 1.77 Å and 1.95 Å, respectively. The PGDH protomer from both species exhibits identical structures, consisting of substrate binding domain and nucleotide binding domain. The residues and water molecules interacting with the NAD are identified. The catalytic triad residues Glu-His-Arg are highly conserved. The residues involved in the dimer interface and the structural features responsible for thermostability are evaluated. Overall, structures of PGDHs with two domains and histidine at the active site are categorized as type III{sub H} and such PGDHs structures having this type are reported for the first time.

  11. Chlamydia pneumoniae CopD Translocator Protein Plays a Critical Role in Type III Secretion (T3S) and Infection

    OpenAIRE

    Bulir, David C.; Waltho, Daniel A.; Stone, Christopher B.; Mwawasi, Kenneth A.; Nelson, Jordan C.; Mahony, James B.

    2014-01-01

    Pathogenic Gram-negative bacteria use type III secretion (T3S) to inject effector proteins into the host cell to create appropriate conditions for infection and intracellular replication. Chlamydia spp. are believed to use T3S to infect their host cell, and the translocator proteins are an essential component of this system. Chlamydia pneumoniae contains genes encoding two sets of translocator proteins; CopB and CopD, and CopB2 and CopD2. In this study, we identified novel interactions betwee...

  12. Salmonella Type III Secretion-Associated Protein InvE Controls Translocation of Effector Proteins into Host Cells

    OpenAIRE

    Kubori, Tomoko; Galán, Jorge E.

    2002-01-01

    Salmonella enterica encodes a type III secretion system (TTSS) within a pathogenicity island located at centisome 63 (SPI-1), which is essential for its pathogenicity. This system mediates the transfer of a battery of bacterial proteins into the host cell with the capacity to modulate cellular functions. The transfer process is dependent on the function of protein translocases SipB, SipC, and SipD. We report here that Salmonella protein InvE, which is also encoded within SPI-1, is essential f...

  13. Crystallization and preliminary crystallographic analysis of a novel plant type III polyketide synthase that produces pentaketide chromone.

    Science.gov (United States)

    Morita, Hiroyuki; Kondo, Shin; Abe, Tsuyoshi; Noguchi, Hiroshi; Sugio, Shigetoshi; Abe, Ikuro; Kohno, Toshiyuki

    2006-09-01

    Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant-specific type III polyketide synthase that catalyzes the formation of 5,7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA. Recombinant PCS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group P2(1), with unit-cell parameters a = 73.2, b = 88.4, c = 70.0 A, alpha = gamma = 90.0, beta = 95.6 degrees . Diffraction data were collected to 1.6 A resolution using synchrotron radiation at BL24XU of SPring-8. PMID:16946474

  14. Design guide for Category III reactors: pool type reactors. [US DOE

    Energy Technology Data Exchange (ETDEWEB)

    Brynda, W J; Lobner, P R; Powell, R W; Straker, E A

    1978-11-01

    The Department of Energy (DOE) in the ERDA Manual requires that all DOE-owned reactors be sited, designed, constructed, modified, operated, maintained, and decommissioned in a manner that gives adequate consideration to health and safety factors. Specific guidance pertinent to the safety of DOE-owned reactors is found in Chapter 0540 of the ERDA Manual. The purpose of this Design Guide is to provide additional guidance to aid the DOE facility contractor in meeting the requirement that the siting, design, construction, modification, operation, maintenance, and decommissioning of DOE-owned reactors be in accordance with generally uniform standards, guides, and codes which are comparable to those applied to similar reactors licensed by the Nuclear Regulatory Commission (NRC). This Design Guide deals principally with the design and functional requirement of Category III reactor structures, components, and systems.

  15. The matlockite-type praseodymium(III oxide bromide PrOBr

    Directory of Open Access Journals (Sweden)

    Pia Talmon-Gros

    2011-12-01

    Full Text Available The crystal structure of the praseodymium(III oxide bromide, PrOBr, can be best described with layers of agglomerated square antiprisms [PrO4Br4]9−. These slabs are stacked along the c axis and linked via two different secondary contacts between Pr3+ and Br−. The Pr3+ cations occupy the Wyckoff site 2c with 4mm symmetry and carry four O2− anions as well as four primary Br− anions, yielding a coordination number of 8. While the Br− anions exhibit the same site symmetry as the Pr3+ cations, the oxide anions are located at the Wyckoff position 2a with site symmetry overline{4}m2 and have four Pr3+ cations as neighbours, defining a tetrahedron.

  16. Deep vein thrombosis, an unreported first manifestation of polyglandular autoimmune syndrome type III

    Science.gov (United States)

    Hogan, P; Oliver, T

    2016-01-01

    Summary A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT) confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA), confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL), decreased serum B12 levels (56pg/mL), with resultant increased methylmalonic acid (5303nmol/L) and hyperhomocysteinemia (131μmol/L), the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD), and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B), defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases. Learning points A DVT can be the first physical manifestation of a polyglandular autoimmune syndrome. Hyperhomocysteinemia secondary to pernicious anemia should be considered as an etiology of an unprovoked DVT in a euthyroid patient with autoimmune thyroid disease. Patients with DVT secondary to hyperhomocysteinemia should undergo screening for the presence of co-existent autoimmune diseases in addition to treatment with B12 supplementation and anticoagulation to prevent recurrent thromboembolism. PMID:27482386

  17. Clonal structure of Trypanosoma cruzi Colombian strain (biodeme Type III: biological, isoenzymic and histopathological analysis of seven isolated clones

    Directory of Open Access Journals (Sweden)

    Camandaroba Edson Luiz Paes

    2001-01-01

    Full Text Available The clonal structure of the Colombian strain of Trypanosoma cruzi, biodeme Type III and zymodeme 1, was analyzed in order to characterize its populations and to establish its homogeneity or heterogeneity. Seven isolated clones presented the basic characteristics of Biodeme Type III, with the same patterns of parasitemic curves, tissue tropism to skeletal muscle and myocardium, high pathogenicity with extensive necrotic-inflammatory lesions from the 20th to 30th day of infection. The parental strain and its clones C1, C3, C4 and C6, determined the higher levels of parasitemia, 20 to 30 days of infection, with high mortality rate up to 30 days (79 to 100%; clones C2, C5 and C7 presented lower levels of parasitemia, with low mortality rates (7.6 to 23%. Isoenzymic patterns, characteristic of zymodeme 1, (Z1 were similar for the parental strain and its seven clones. Results point to a phenotypic homogeneity of the clones isolated from the Colombian strain and suggest the predominance of a principal clone, responsible for the biological behavior of the parental strain and clones.

  18. Nuclear Magnetic Resonance Characterization of the Type III Secretion System Tip Chaperone Protein PcrG of Pseudomonas aeruginosa.

    Science.gov (United States)

    Chaudhury, Sukanya; Nordhues, Bryce A; Kaur, Kawaljit; Zhang, Na; De Guzman, Roberto N

    2015-11-01

    Lung infection with Pseudomonas aeruginosa is the leading cause of death among cystic fibrosis patients. To initiate infection, P. aeruginosa assembles a protein nanomachine, the type III secretion system (T3SS), to inject bacterial proteins directly into target host cells. An important regulator of the P. aeruginosa T3SS is the chaperone protein PcrG, which forms a complex with the tip protein, PcrV. In addition to its role as a chaperone to the tip protein, PcrG also regulates protein secretion. PcrG homologues are also important in the T3SS of other pathogens such as Yersinia pestis, the causative agent of bubonic plague. The atomic structure of PcrG or any member of the family of tip protein chaperones is currently unknown. Here, we show by circular dichroism and nuclear magnetic resonance (NMR) spectroscopy that PcrG lacks a tertiary structure. However, it is not completely disordered but contains secondary structures dominated by two long α-helices from residue 16 to 41 and from residue 55 to 76. The helices of PcrG are partially formed, have similar backbone dynamics, and are flexible. NMR titrations show that the entire length of PcrG residues from position 9 to 76 is involved in binding to PcrV. PcrG adds to the growing list of partially folded or unstructured proteins with important roles in type III secretion.

  19. A Decade of Solar Type III Radio Bursts Observed by the Nançay Radioheliograph 1998-2008

    Science.gov (United States)

    Saint-Hilaire, P.; Vilmer, N.; Kerdraon, A.

    2013-01-01

    We present a statistical survey of almost 10,000 radio type III bursts observed by the Nançay Radioheliograph from 1998 to 2008, covering nearly a full solar cycle. In particular, sources sizes, positions, and fluxes were examined. We find an east-west asymmetry in source positions that could be attributed to a 6° ± 1° eastward tilt of the magnetic field, that source FWHM sizes s roughly follow a solar-cycle-averaged distribution (dN/ds) ≈ 14 ν-3.3 s -4 arcmin-1 day-1, and that source fluxes closely follow a solar-cycle-averaged (dN/ds ν) ≈ 0.34 ν-2.9 S -1.7 ν sfu-1 day-1 distribution (when ν is in GHz, s in arcminutes, and S ν in sfu). Fitting a barometric density profile yields a temperature of 0.6 MK, while a solar wind-like (vproph -2) density profile yields a density of 1.2 × 106 cm-3 at an altitude of 1 RS , assuming harmonic emission. Finally, we found that the solar-cycle-averaged radiated type III energy could be similar in magnitude to that radiated by nanoflares via non-thermal bremsstrahlung processes, and we hint at the possibility that escaping electron beams might carry as much energy away from the corona as is introduced into it by accelerated nanoflare electrons.

  20. Neutrinoless Double Beta Decay in Type I+II Seesaw Models

    CERN Document Server

    Borah, Debasish

    2015-01-01

    We study neutrinoless double beta decay in left-right symmetric extension of the standard model with type I and type II seesaw origin of neutrino masses. Due to the enhanced gauge symmetry as well as extended scalar sector, there are several new physics sources of neutrinoless double beta decay in this model. Ignoring the left-right gauge boson mixing and heavy-light neutrino mixing, we first compute the contributions to neutrinoless double beta decay for type I and type II dominant seesaw separately and compare with the standard light neutrino contributions. We then repeat the exercise by considering the presence of both type I and type II seesaw, having non-negligible contributions to light neutrino masses and show the difference in results from individual seesaw cases. Assuming the new gauge bosons and scalars to be around a TeV, we constrain different parameters of the model including both heavy and light neutrino masses from the requirement of keeping the neutrinoless double beta decay amplitude below th...

  1. Neutrinoless double beta decay in type I+II seesaw models

    Science.gov (United States)

    Borah, Debasish; Dasgupta, Arnab

    2015-11-01

    We study neutrinoless double beta decay in left-right symmetric extension of the standard model with type I and type II seesaw origin of neutrino masses. Due to the enhanced gauge symmetry as well as extended scalar sector, there are several new physics sources of neutrinoless double beta decay in this model. Ignoring the left-right gauge boson mixing and heavy-light neutrino mixing, we first compute the contributions to neutrinoless double beta decay for type I and type II dominant seesaw separately and compare with the standard light neutrino contributions. We then repeat the exercise by considering the presence of both type I and type II seesaw, having non-negligible contributions to light neutrino masses and show the difference in results from individual seesaw cases. Assuming the new gauge bosons and scalars to be around a TeV, we constrain different parameters of the model including both heavy and light neutrino masses from the requirement of keeping the new physics contribution to neutrinoless double beta decay amplitude below the upper limit set by the GERDA experiment and also satisfying bounds from lepton flavor violation, cosmology and colliders.

  2. The Galactic O-Star Spectroscopic Survey (GOSSS). III. 142 additional O-type systems

    CERN Document Server

    Apellániz, J Maíz; Arias, J I; Barbá, R H; Walborn, N R; Simón-Díaz, S; Negueruela, I; Marco, A; Leão, J R S; Herrero, A; Gamen, R C; Alfaro, E J

    2016-01-01

    This is the third installment of GOSSS, a massive spectroscopic survey of Galactic O stars, based on new homogeneous, high signal-to-noise ratio, R~2500 digital observations selected from the Galactic O-Star Catalog (GOSC). In this paper we present 142 additional stellar systems with O stars from both hemispheres, bringing the total of O-type systems published within the project to 590. Among the new objects there are 20 new O stars. We also identify 11 new double-lined spectroscopic binaries (SB2s), of which 6 are of O+O type and 5 of O+B type, and an additional new tripled-lined spectroscopic binary (SB3) of O+O+B type. We also revise some of the previous GOSSS classifications, present some egregious examples of stars erroneously classified as O-type in the past, introduce the use of luminosity class IV at spectral types O4-O5.5, and adapt the classification scheme to the work of Arias et al. (2016).

  3. Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction

    Directory of Open Access Journals (Sweden)

    Kinnamon Sue C

    2001-04-01

    Full Text Available Abstract Background Taste receptor cells are responsible for transducing chemical stimuli into electrical signals that lead to the sense of taste. An important second messenger in taste transduction is IP3, which is involved in both bitter and sweet transduction pathways. Several components of the bitter transduction pathway have been identified, including the T2R/TRB taste receptors, phospholipase C β2, and the G protein subunits α-gustducin, β3, and γ13. However, the identity of the IP3 receptor subtype in this pathway is not known. In the present study we used immunocytochemistry on rodent taste tissue to identify the IP3 receptors expressed in taste cells and to examine taste bud expression patterns for IP3R3. Results Antibodies against Type I, II, and III IP3 receptors were tested on sections of rat and mouse circumvallate papillae. Robust cytoplasmic labeling for the Type III IP3 receptor (IP3R3 was found in a large subset of taste cells in both species. In contrast, little or no immunoreactivity was seen with antibodies against the Type I or Type II IP3 receptors. To investigate the potential role of IP3R3 in bitter taste transduction, we used double-label immunocytochemistry to determine whether IP3R3 is expressed in the same subset of cells expressing other bitter signaling components. IP3R3 immunoreactive taste cells were also immunoreactive for PLCβ2 and γ13. Alpha-gustducin immunoreactivity was present in a subset of IP3R3, PLCβ2, and γ13 positive cells. Conclusions IP3R3 is the dominant form of the IP3 receptor expressed in taste cells and our data suggest it plays an important role in bitter taste transduction.

  4. Type 1 AGN at low z. III. The optical narrow line ratios

    CERN Document Server

    Stern, Jonathan

    2012-01-01

    We present the optical narrow line ratios in an SDSS based sample of 3,175 broad Ha selected type 1 AGN, and explore their positions in the BPT diagrams as a function of the AGN and the host properties. We find the following: 1. The luminosities of all measured narrow lines (Ha, Hb, [OIII], [NII], [SII], [OI]) show a Baldwin relation relative to the broad Ha luminosity L_bHa, with slopes in the range of 0.53-0.72. 2. About 20% of the type 1 AGN reside within the `Composite' and `SF' regions of the BPT diagrams. These objects also show excess narrow Ha and UV luminosities, for their L_bHa, consistent with contribution from star formation which dominates the narrow lines emission, as expected from their positions in the BPT diagrams. 3. The type 1 which reside within the AGN region in the BPT diagrams, are offset to lower [SII]/Ha and [NII]/Ha luminosity ratios, compared to type 2 AGN. This offset is a selection effect, related to the lower AGN/host luminosity selection of the type 2 AGN selected from the SDSS ...

  5. The Galactic O-Star Spectroscopic Survey (GOSSS). III. 142 Additional O-type Systems.

    Science.gov (United States)

    Maíz Apellániz, J.; Sota, A.; Arias, J. I.; Barbá, R. H.; Walborn, N. R.; Simón-Díaz, S.; Negueruela, I.; Marco, A.; Leão, J. R. S.; Herrero, A.; Gamen, R. C.; Alfaro, E. J.

    2016-05-01

    This is the third installment of the Galactic O-Star Spectroscopic Survey (GOSSS), a massive spectroscopic survey of Galactic O stars, based on new homogeneous, high signal-to-noise ratio, R ∼ 2500 digital observations selected from the Galactic O-Star Catalog. In this paper, we present 142 additional stellar systems with O stars from both hemispheres, bringing the total of O-type systems published within the project to 590. Among the new objects, there are 20 new O stars. We also identify 11 new double-lined spectroscopic binaries, 6 of which are of O+O type and 5 of O+B type, and an additional new tripled-lined spectroscopic binary of O+O+B type. We also revise some of the previous GOSSS classifications, present some egregious examples of stars erroneously classified as O-type in the past, introduce the use of luminosity class IV at spectral types O4-O5.5, and adapt the classification scheme to the work of Arias et al. The GOSSS spectroscopic data in this article were gathered with five facilities: the 1.5 m Telescope at the Observatorio de Sierra Nevada (OSN), the 2.5 m du Pont Telescope at Las Campanas Observatory (LCO), the 3.5 m Telescope at Calar Alto Observatory (CAHA), and the 4.2 m William Herschel Telescope (WHT) and 10.4 m Gran Telescopio Canarias (GTC) at Observatorio del Roque de los Muchachos (ORM).

  6. Neutrino Masses and Leptogenesis in Type I+II Seesaw Models

    OpenAIRE

    Borah, Debasish; Das, Mrinal Kumar

    2013-01-01

    The baryon to photon ratio in the present Universe is very accurately measured to be $(6.065 \\pm 0.090) \\times 10^{-10}$. We study the possible origin of this baryon asymmetry in the neutrino sector through the generic mechanism of baryogenesis through leptogenesis. We consider both type I and type II seesaw origin of neutrino masses within the framework of left right symmetric models (LRSM). Using the latest best fit global neutrino oscillation data of mass squared differences, mixing angles...

  7. Acute downregulation of Type II and Type III iodothyronine deiodinases by photoperiod in peripubertal male and female Siberian hamsters.

    Science.gov (United States)

    Kampf-Lassin, August; Prendergast, Brian J

    2013-11-01

    Availability of the thyroid hormone triiodothyronine (T3) in the mediobasal hypothalamus plays a central role in seasonal reproductive responses to photoperiod. Across many vertebrates, Type 2 iodothyronine deiodinase (DIO2) is elevated under reproductively stimulatory long days (LD) and synthesizes the conversion of thyroxine to T3; Type 3 iodothyronine deiodinase (DIO3) reduces T3 production and signaling, and is upregulated under reproductively-inhibitory short days (SD). In Siberian hamsters, regulation of hypothalamic T3 is dominated by dio3 expression, whereas dio2 expression is less-consistently affected by photoperiod. In adult hamsters, changes in deiodinase mRNA expression typically require several weeks to manifest, but it is not known whether or how quickly these mechanisms are engaged during the rapid responses to photoperiod observed in young, peri-pubertal hamsters. This experiment tested the hypotheses that (1) deiodinase responses to photoperiod are accelerated in juvenile hamsters and (2) photoperiodic downregulation of deiodinase expression occurs more rapidly than upregulation. Hypothalamic dio2 and dio3 mRNA expression was quantified in male and female Siberian hamsters that were weaned on postnatal day 18 (PND 18) into SD or remained in their natal LD, and on PND 31 were exposed to a single long or short day. In SD males and females, a single long day inhibited dio3 mRNA expression, but did not increase dio2 mRNA. In LD males, a single short day rapidly inhibited dio2 mRNA expression, but did not stimulate expression of dio3 mRNA. Downregulation of dio2 and dio3 mRNAs precedes gonadotrophin responses to day length. Rapid photoperiodic inhibition of deiodinase mRNAs may initiate changes in thyroid hormone signaling in advance of longer-term, melatonin-dependent, responses.

  8. High Dispersion Spectroscopy of Solar-type Superflare Stars. III. Lithium Abundances

    CERN Document Server

    Honda, Satoshi; Maehara, Hiroyuki; Notsu, Shota; Shibayama, Takuya; Nogami, Daisaku; Shibata, Kazunari

    2015-01-01

    We report on the abundance analysis of Li in solar-type (G-type main sequence) superflare stars which were found by the analysis of Kepler photometric data. Li is a key element to understand the evolution of the stellar convection zone which reflects the age of solar-type stars. We performed the high dispersion spectroscopy of solar-type superflare stars with Subaru/HDS, and confirmed that 34 stars show no evidence of binarity in our previous study. In this study, we derived the Li abundances of these 34 objects. We investigate correlations of Li abundance with stellar atmospheric parameters, rotational velocity, and superflare activities to understand the nature of superflare stars and the possibility of the nucleosynthesis of Li by superflares. We confirm the large dispersion in the Li abundance, and the correlation with stellar parameters is not seen. As compared with the Li abundance in Hyades cluster which is younger than the Sun, it is suggested that half of the observed stars are younger than Hyades cl...

  9. Galaxy populations in the Antlia cluster - III. Properties of faint early-type galaxies

    CERN Document Server

    Castelli, Analia V Smith; Faifer, Favio R; Bassino, Lilia P; Richtler, Tom; Romero, Gisela A; Calderon, Juan Pablo; Caso, Juan Pablo

    2011-01-01

    (Abridge) We present a new analysis of the early-type galaxy population in the central region of the Antlia cluster, focusing on the faint systems like dwarf ellipticals (dE) and dwarf spheroidals (dSph). We confirm 22 early-type galaxies as Antlia members, using GEMINI-GMOS and MAGELLAN-MIKE spectra. Among them, 2 belong to the rare type of compact ellipticals (cE), and 5 are new faint dwarfs that had never been catalogued before. In addition, we present 16 newly identified low surface brightness galaxy candidates, almost half of them displaying morphologies consistent with being Antlia's counterparts of Local Group dSphs, that extend the faint luminosity limit of our study down to MB = -10.1 (BT = 22.6) mag. We built an improved CMR in the Washington photometric system, i.e. integrated T1 magnitudes versus (C - T1) colours, which extends \\sim 4 mag faintwards the limit of spectroscopically confirmed Antlia members. When only confirmed early-type members are considered, this relation extends over 10 mag in l...

  10. Type III interferon protects swine against foot-and-mouth disease

    Science.gov (United States)

    In recent years we have developed novel strategies to control foot-and-mouth disease (FMD) including the use of biotherapeutics such as interferons (IFN) delivered by a replication-defective human adenovirus type 5 (Ad5). Swine can be sterilely protected after vaccination with an Ad5 that encodes po...

  11. Neonatal infection with neurotropic influenza A virus affects working memory and expression of type III Nrg1 in adult mice.

    Science.gov (United States)

    Asp, Linnéa; Beraki, Simret; Kristensson, Krister; Ogren, Sven Ove; Karlsson, Håkan

    2009-08-01

    Epidemiological studies suggest that early life infections may contribute to the development of psychiatric disorders characterized by cognitive deficits. Here, we studied the effects of a neonatal influenza A/WSN/33 virus infection on locomotor activity, working memory and emotional behavior in adult mice. In addition to wild type mice, immunodeficient (Tap1(-/-)) mice lacking functional CD8(+) T cells, were included in the study to model the potential influence of a genetic deficit relating to virus clearance. Three to four months after the infection, infected Tap1(-/-) mice, but not wild type mice, exhibited deficits in working memory as well as increased rearing activity and anxiety. In the medial prefrontal cortices of these infected Tap1(-/-) mice reduced levels of type III Nrg1 transcripts were observed supporting a role for neuregulin 1 signaling in neuronal circuits involved in working memory. Virus replication, distribution or clearance did not differ between the two genotypes. The lack of CD8(+) T cells, however, appeared to contribute to a more pronounced glia response in Tap1(-/-) than in wild type mice. Thus, the present study suggest that the risk of developing deficits in cognitive and emotional behavior following a CNS infection during brain development is influenced by genetic variation in genes involved in the immune response.

  12. On the molecular basis of D-bifunctional protein deficiency type III.

    Directory of Open Access Journals (Sweden)

    Maija L Mehtälä

    Full Text Available Molecular basis of D-bifunctional protein (D-BP deficiency was studied with wild type and five disease-causing variants of 3R-hydroxyacyl-CoA dehydrogenase fragment of the human MFE-2 (multifunctional enzyme type 2 protein. Complementation analysis in vivo in yeast and in vitro enzyme kinetic and stability determinants as well as in silico stability and structural fluctuation calculations were correlated with clinical data of known patients. Despite variations not affecting the catalytic residues, enzyme kinetic performance (K(m, V(max and k(cat of the recombinant protein variants were compromised to a varying extent and this can be judged as the direct molecular cause for D-BP deficiency. Protein stability plays an additional role in producing non-functionality of MFE-2 in case structural variations affect cofactor or substrate binding sites. Structure-function considerations of the variant proteins matched well with the available data of the patients.

  13. Potential efficacy of enzyme replacement and substrate reduction therapy in three siblings with Gaucher disease type III.

    Science.gov (United States)

    Cox-Brinkman, J; van Breemen, M J; van Maldegem, B T; Bour, L; Donker, W E; Hollak, C E M; Wijburg, F A; Aerts, J M F G

    2008-12-01

    We report three siblings with Gaucher disease type III, born between 1992 and 2004. During this period, new developments resulted in different potential therapies, changing clinical practice. The two eldest siblings received enzyme replacement therapy (ERT) from the age of 24 and 5 months respectively, later followed by an increase in dosage. ERT was combined with substrate reduction therapy (SRT) from the ages of 12 and 8 years, respectively. In the youngest sibling the combination of high-dose ERT and SRT was given from the age of 5 months. The two eldest siblings showed significant neurological impairment from the age of 1.5 years, starting with a convergent strabismus and partial oculomotor apraxia, followed by cognitive decline and an abnormal EEG and BAER. In contrast, the neurological development in the youngest sibling is almost completely normal. At the age of 3 years, cognitive development, EEG and BAER are all normal. Disturbed saccadic eye movements, which were already present at the start of therapy, remained stable. In addition to the clinical efficacy, we report on the biochemical response to therapy. Based on our results, the combination of high-dose ERT and SRT should be considered as a possible therapeutic approach for GD III, especially if started at a young age. Further follow-up studies are necessary to explore the long-term therapeutic effects. PMID:18850301

  14. Conversion from electron plasma waves to type III solar radio bursts with 'HELIOS' observations

    International Nuclear Information System (INIS)

    The purpose of this paper is to introduce new HELIOS observation which confirm the basic mechanism of type 3 solar radio bursts and then to compare them with ground and/or near earth satellite observations. It is considered that the bursts are generated by a two-step process. The process is the production of localized electron plasma oscillation and the conversion of this plasma oscillation to escaping electromagnetic radiation. Variations of the characteristic frequency of solar radio bursts come from the gradual decrease in the electron plasma frequency encountered. Examples of the temporal distributions of electron plasma oscillations and associated type 3 solar radio bursts are shown. The so-called ''forward drift'' is seen. Another example shows that the burst sources are distributed along a spiral magnetic field in the interplanetary space. The result of comparison of conventional ground and recent HELIOS observations is presented. The frequency range of the type 3 bursts is from 10 to 200 kHz in case of HELIOS, which is much lower than the frequency observed on the ground. Source location, dynamic spectrum, duration time of burst, drift rate, flare electron velocity, electron plasma oscillation, location of EPO or solar flare electrons, intensities of fundamental and harmonic frequencies, and polarization were also compared between ground and HELIOS observations. (Kato, T.)

  15. C-type lectin-like carbohydrate recognition of the hemolytic lectin CEL-III containing ricin-type -trefoil folds.

    Science.gov (United States)

    Hatakeyama, Tomomitsu; Unno, Hideaki; Kouzuma, Yoshiaki; Uchida, Tatsuya; Eto, Seiichiro; Hidemura, Haruki; Kato, Norihisa; Yonekura, Masami; Kusunoki, Masami

    2007-12-28

    CEL-III is a Ca(2+)-dependent hemolytic lectin, isolated from the marine invertebrate Cucumaria echinata. The three-dimensional structure of CEL-III/GalNAc and CEL-III/methyl alpha-galactoside complexes was solved by x-ray crystallographic analysis. In these complexes, five carbohydrate molecules were found to be bound to two carbohydrate-binding domains (domains 1 and 2) located in the N-terminal 2/3 portion of the polypeptide and that contained beta-trefoil folds similar to ricin B-chain. The 3-OH and 4-OH of bound carbohydrate molecules were coordinated with Ca(2+) located at the subdomains 1alpha, 1gamma, 2alpha, 2beta, and 2gamma, simultaneously forming hydrogen bond networks with nearby amino acid side chains, which is similar to carbohydrate binding in C-type lectins. The binding of carbohydrates was further stabilized by aromatic amino acid residues, such as tyrosine and tryptophan, through a stacking interaction with the hydrophobic face of carbohydrates. The importance of amino acid residues in the carbohydrate-binding sites was confirmed by the mutational analyses. The orientation of bound GalNAc and methyl alpha-galactoside was similar to the galactose moiety of lactose bound to the carbohydrate-binding site of the ricin B-chain, although the ricin B-chain does not require Ca(2+) ions for carbohydrate binding. The binding of the carbohydrates induced local structural changes in carbohydrate-binding sites in subdomains 2alpha and 2beta. Binding of GalNAc also induced a slight change in the main chain structure of domain 3, which could be related to the conformational change upon binding of specific carbohydrates to induce oligomerization of the protein. PMID:17977832

  16. Tissue elasticity displayed by elastography and its correlation with the characteristics of collagen type I and type III in prostatic stroma

    Directory of Open Access Journals (Sweden)

    Jie Tang

    2014-04-01

    Full Text Available We investigated the prostate elasticity displayed by elastography and its correlation with the content and distribution of collagen type I (Col1 and type III (Col3. A total of 62 patients underwent transrectal real-time tissue elastography (TRTE examinations. Targeted biopsies were performed after 12-core systematic biopsy. The tissues corresponding to the elastograms were stained with picric acid-sirius red. The distribution of Col1 and type Col3 was observed, and the collagen volume fraction (CVF of these two types of collagen fibers was calculated. The CVFs of Col1 in the stiff and soft groups were 0.05 ± 0.02 and 0.02 ± 0.01 (P = 0.002, respectively. The CVFs of Col3 in the stiff and soft groups were 0.05 ± 0.04 and 0.07 ± 0.03 (P = 0.13, respectively. The circular analysis results showed that collagen fibers were disorganized both in the soft and stiff groups. Col1 and Col3 were mainly cross-linked, and some parallelization was observed in the sections. The distributions of Col1 and Col3 were different between the stiff and soft groups (P = 0.03. In conclusion, the texture of the prostate is due to the content of Col1 and its relative correlation with Col3.

  17. Domains and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I-III and V

    OpenAIRE

    Colige, Alain; Ruggiero, Florence; Vandenberghe, Isabel; Dubail, Johanne; Kesteloot, Frédéric; Van Beeumen, Jozef; Beschin, Alain; Brys, Lea; Lapière, Charles M.; Nusgens, Betty

    2005-01-01

    Processing of fibrillar collagens is required to generate collagen monomers able to self-assemble into elongated and cylindrical collagen fibrils. ADAMTS-2 belongs to the "A disintegrin and metalloproteinase with thrombospondin type 1 motifs" (ADAMTS) family. It is responsible for most of the processing of the aminopropeptide of type I procollagen in the skin, and it also cleaves type II and type III procollagens. ADAMTS are complex secreted enzymes that are implicated in various physiologica...

  18. An archaeal CRISPR type III-B system exhibiting distinctive RNA targeting features and mediating dual RNA and DNA interference

    DEFF Research Database (Denmark)

    Peng, Wenfang; Feng, Mingxia; Feng, Xu;

    2015-01-01

    CRISPR-Cas systems provide a small RNA-based mechanism to defend against invasive genetic elements in archaea and bacteria. To investigate the in vivo mechanism of RNA interference by two type III-B systems (Cmr-α and Cmr-β) in Sulfolobus islandicus, a genetic assay was developed using plasmids...... carrying an artificial mini-CRISPR (AC) locus with a single spacer. After pAC plasmids were introduced into different strains, Northern analyses confirmed that mature crRNAs were produced from the plasmid-borne CRISPR loci, which then guided gene silencing to target gene expression. Spacer mutagenesis....... islandicus Cmr-α mediated transcription-dependent DNA interference, the Cmr-α constitutes the first CRISPR system exhibiting dual targeting of RNA and DNA....

  19. Crystallization and preliminary crystallographic analysis of a novel plant type III polyketide synthase that produces pentaketide chromone

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Hiroyuki [Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511 (Japan); Kondo, Shin [ZOEGENE Corporation, 1000 Kamoshida, Aoba, Yokohama, Kanagawa 227-8502 (Japan); Abe, Tsuyoshi; Noguchi, Hiroshi [School of Pharmaceutical Sciences and the COE21 Program, University of Shizuoka, Shizuoka 422-8526 (Japan); Sugio, Shigetoshi, E-mail: ssugio@rc.m-kagaku.co.jp [ZOEGENE Corporation, 1000 Kamoshida, Aoba, Yokohama, Kanagawa 227-8502 (Japan); Abe, Ikuro, E-mail: ssugio@rc.m-kagaku.co.jp [School of Pharmaceutical Sciences and the COE21 Program, University of Shizuoka, Shizuoka 422-8526 (Japan); PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kohno, Toshiyuki, E-mail: ssugio@rc.m-kagaku.co.jp [Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511 (Japan)

    2006-09-01

    Pentaketide chromone synthase from A. arborescens has been overexpressed in E. coli, purified and crystallized. Diffraction data have been collected to 1.6 Å. Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant-specific type III polyketide synthase that catalyzes the formation of 5,7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA. Recombinant PCS expressed in Escherichia coli was crystallized by the hanging-drop vapour-diffusion method. The crystals belonged to space group P2{sub 1}, with unit-cell parameters a = 73.2, b = 88.4, c = 70.0 Å, α = γ = 90.0, β = 95.6°. Diffraction data were collected to 1.6 Å resolution using synchrotron radiation at BL24XU of SPring-8.

  20. Serum type III procollagen peptide in patients with Pneumocystis carinii infection. The Copenhagen-Amsterdam PCP-Prednisolone Study Group

    DEFF Research Database (Denmark)

    Bentsen, K D; Nielsen, T L; Eaftinck Schattenkerk, J K;

    1993-01-01

    Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders. To...... investigate changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive serum samples were taken from 48 HIV-infected patients with PCP in a randomized, placebo-controlled study of the effect of adjunctive methylprednisolone therapy (26 in corticosteroid [CS] group and 22 in control group...... steroid was administered. At Days 21 to 28 there were no difference in the levels of PIIINP between the two groups. PIIINP serum levels may predict the clinical outcome of PCP. The antimicrobial therapy may exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory failure. CS...

  1. Inhibition of a type III secretion system by the deletion of a short loop in one of its membrane proteins

    International Nuclear Information System (INIS)

    Crystal structures of the cytoplasmic domain of FlhB from S. typhimurium and A. aeolicus were solved at 2.45 and 2.55 Å resolution, respectively. The deletion of a short loop in the cytoplasmic domain of Salmonella FlhB completely abolishes secretion by the type III secretion system. A molecular-dynamics simulation shows that the deletion of the loop affects the flexibility of a linker between the transmembrane and cytoplasmic domains of FlhB. The membrane protein FlhB is a highly conserved component of the flagellar secretion system. It is composed of an N-terminal transmembrane domain and a C-terminal cytoplasmic domain (FlhBC). Here, the crystal structures of FlhBC from Salmonella typhimurium and Aquifex aeolicus are described at 2.45 and 2.55 Å resolution, respectively. These flagellar FlhBC structures are similar to those of paralogues from the needle type III secretion system, with the major difference being in a linker that connects the transmembrane and cytoplasmic domains of FlhB. It was found that deletion of a short flexible loop in a globular part of Salmonella FlhBC leads to complete inhibition of secretion by the flagellar secretion system. Molecular-dynamics calculations demonstrate that the linker region is the most flexible part of FlhBC and that the deletion of the loop reduces this flexibility. These results are in good agreement with previous studies showing the importance of the linker in the function of FlhB and provide new insight into the relationship between the different parts of the FlhBC molecule

  2. Near-atomic resolution analysis of BipD, a component of the type III secretion system of Burkholderia pseudomallei

    International Nuclear Information System (INIS)

    The type III secretion system needle-tip protein BipD has been crystallized in a form that diffracts X-rays to 1.5 Å resolution and the structure has been refined to an R factor of 16.1% and an Rfree of 19.8% at this resolution. The putative antiparallel dimer interface that was observed in earlier structures is conserved. Burkholderia pseudomallei, the causative agent of melioidosis, possesses a type III protein secretion apparatus that is similar to those found in Salmonella and Shigella. A major function of these secretion systems is to inject virulence-associated proteins into target cells of the host organism. The bipD gene of B. pseudomallei encodes a secreted virulence factor that is similar in sequence and is most likely to be functionally analogous to IpaD from Shigella and SipD from Salmonella. Proteins in this family are thought to act as extracellular chaperones at the tip of the secretion needle to help the hydrophobic translocator proteins enter the target cell membrane, where they form a pore and may also link the translocon pore with the secretion needle. BipD has been crystallized in a monoclinic crystal form that diffracted X-rays to 1.5 Å resolution and the structure was refined to an R factor of 16.1% and an Rfree of 19.8% at this resolution. The putative dimer interface that was observed in previous crystal structures was retained and a larger surface area was buried in the new crystal form

  3. Inhibition of a type III secretion system by the deletion of a short loop in one of its membrane proteins

    Energy Technology Data Exchange (ETDEWEB)

    Meshcheryakov, Vladimir A. [Okinawa Instiute of Science and Technology, Okinawa 904-0495 (Japan); Kitao, Akio [University of Tokyo, Tokyo 113-0032 (Japan); Core Research for Evolutionary Science and Technology, Tokyo 113-0032 (Japan); Matsunami, Hideyuki; Samatey, Fadel A., E-mail: f.a.samatey@oist.jp [Okinawa Instiute of Science and Technology, Okinawa 904-0495 (Japan)

    2013-05-01

    Crystal structures of the cytoplasmic domain of FlhB from S. typhimurium and A. aeolicus were solved at 2.45 and 2.55 Å resolution, respectively. The deletion of a short loop in the cytoplasmic domain of Salmonella FlhB completely abolishes secretion by the type III secretion system. A molecular-dynamics simulation shows that the deletion of the loop affects the flexibility of a linker between the transmembrane and cytoplasmic domains of FlhB. The membrane protein FlhB is a highly conserved component of the flagellar secretion system. It is composed of an N-terminal transmembrane domain and a C-terminal cytoplasmic domain (FlhB{sub C}). Here, the crystal structures of FlhB{sub C} from Salmonella typhimurium and Aquifex aeolicus are described at 2.45 and 2.55 Å resolution, respectively. These flagellar FlhB{sub C} structures are similar to those of paralogues from the needle type III secretion system, with the major difference being in a linker that connects the transmembrane and cytoplasmic domains of FlhB. It was found that deletion of a short flexible loop in a globular part of Salmonella FlhB{sub C} leads to complete inhibition of secretion by the flagellar secretion system. Molecular-dynamics calculations demonstrate that the linker region is the most flexible part of FlhB{sub C} and that the deletion of the loop reduces this flexibility. These results are in good agreement with previous studies showing the importance of the linker in the function of FlhB and provide new insight into the relationship between the different parts of the FlhB{sub C} molecule.

  4. Identification of small-molecule inhibitors of Yersinia pestis Type III secretion system YscN ATPase.

    Directory of Open Access Journals (Sweden)

    Wieslaw Swietnicki

    Full Text Available Yersinia pestis is a gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain of the yscN gene in Y. pestis CO92 attenuated the strain over three million-fold in the Swiss-Webster mouse model of bubonic plague. The result validates the YscN protein as a therapeutic target for plague. The catalytic domain of the YscN protein was made using recombinant methods and its ATPase activity was characterized in vitro. To identify candidate therapeutics, we tested computationally selected small molecules for inhibition of YscN ATPase activity. The best inhibitors had measured IC(50 values below 20 µM in an in vitro ATPase assay and were also found to inhibit the homologous BsaS protein from Burkholderia mallei animal-like T3SS at similar concentrations. Moreover, the compounds fully inhibited YopE secretion by attenuated Y. pestis in a bacterial cell culture and mammalian cells at µM concentrations. The data demonstrate the feasibility of targeting and inhibiting a critical protein transport ATPase of a bacterial virulence system. It is likely the same strategy could be applied to many other common human pathogens using type III secretion system, including enteropathogenic E. coli, Shigella flexneri, Salmonella typhimurium, and Burkholderia mallei/pseudomallei species.

  5. The Structures of Coiled-Coil Domains from Type III Secretion System Translocators Reveal Homology to Pore-Forming Toxins

    Energy Technology Data Exchange (ETDEWEB)

    Barta, Michael L.; Dickenson, Nicholas E.; Patil, Mrinalini; Keightley, Andrew; Wyckoff, Gerald J.; Picking, William D.; Picking, Wendy L.; Geisbrecht, Brian V. (UMKC); (OKLU)

    2012-03-26

    Many pathogenic Gram-negative bacteria utilize type III secretion systems (T3SSs) to alter the normal functions of target cells. Shigella flexneri uses its T3SS to invade human intestinal cells to cause bacillary dysentery (shigellosis) that is responsible for over one million deaths per year. The Shigella type III secretion apparatus is composed of a basal body spanning both bacterial membranes and an exposed oligomeric needle. Host altering effectors are secreted through this energized unidirectional conduit to promote bacterial invasion. The active needle tip complex of S. flexneri is composed of a tip protein, IpaD, and two pore-forming translocators, IpaB and IpaC. While the atomic structure of IpaD has been elucidated and studied, structural data on the hydrophobic translocators from the T3SS family remain elusive. We present here the crystal structures of a protease-stable fragment identified within the N-terminal regions of IpaB from S. flexneri and SipB from Salmonella enterica serovar Typhimurium determined at 2.1 {angstrom} and 2.8 {angstrom} limiting resolution, respectively. These newly identified domains are composed of extended-length (114 {angstrom} in IpaB and 71 {angstrom} in SipB) coiled-coil motifs that display a high degree of structural homology to one another despite the fact that they share only 21% sequence identity. Further structural comparisons also reveal substantial similarity to the coiled-coil regions of pore-forming proteins from other Gram-negative pathogens, notably, colicin Ia. This suggests that these mechanistically separate and functionally distinct membrane-targeting proteins may have diverged from a common ancestor during the course of pathogen-specific evolutionary events.

  6. Enzymes of collagen synthesis and type III procollagen aminopropeptide in the evaluation of D-penicillamine and medroxyprogesterone treatments of primary biliary cirrhosis.

    OpenAIRE

    Savolainen, E R; Miettinen, T A; Pikkarainen, P.; Salaspuro, M P; Kivirikko, K I

    1983-01-01

    Changes in serum immunoreactive prolyl hydroxylase protein (IRPH), galactosylhydroxylysyl glucosyltransferase activity (GGT) and the aminoterminal propeptide of type III procollagen [Pro(III)-N-P] were studied in 21 patients with primary biliary cirrhosis during a follow-up period of up to three years. The patients received either D-penicillamine (600 mg/day), medroxyprogesterone acetate (5 mg/day), or a placebo, or no treatment after the D-penicillamine or medroxyprogesterone medication, eac...

  7. All-optical digital 4 × 2 encoder based on 2D photonic crystal ring resonators

    Science.gov (United States)

    Moniem, Tamer A.

    2016-04-01

    The photonic crystals draw significant attention to build all-optical logic devices and are considered one of the solutions for the opto-electronic bottleneck via speed and size. The paper presents a novel optical 4 × 2 encoder based on 2D square lattice photonic crystals of silicon rods. The main realization of optical encoder is based on the photonic crystal ring resonator NOR gates. The proposed structure has four logic input ports, two output ports, and two bias input port. The photonic crystal structure has a square lattice of silicon rods with a refractive index of 3.39 in air. The structure has lattice constant 'a' equal to 630 nm and bandgap range from 0.32 to 044. The total size of the proposed 4 × 2 encoder is equal to 35 μm × 35 μm. The simulation results using the dimensional finite difference time domain and Plane Wave Expansion methods confirm the operation and the feasibility of the proposed optical encoder for ultrafast optical digital circuits.

  8. SPIDER - III. Environmental dependence of the Fundamental Plane of early-type galaxies

    Science.gov (United States)

    La Barbera, F.; Lopes, P. A. A.; de Carvalho, R. R.; de La Rosa, I. G.; Berlind, A. A.

    2010-11-01

    We analyse the Fundamental Plane (FP) relation of 39993 early-type galaxies (ETGs) in the optical (griz) and 5080 ETGs in the near-infrared (NIR; YJHK) wavebands, forming an optical+NIR sample of 4589 galaxies. We focus on the analysis of the FP as a function of the environment where galaxies reside. We characterize the environment using the largest group catalogue, based on 3D data, generated from the Sloan Digital Sky Survey at low redshift (z population properties with mass in ETGs is shallower for galaxies at high density, resulting from tidal stripping and quenching of star formation in galaxies falling into the group's potential well. We do not detect any dependence of the FP coefficients on the presence of substructures in parent galaxy groups.

  9. Specific inhibition of secreted NRG1 types I-II by heparin enhances Schwann Cell myelination.

    Science.gov (United States)

    Eshed-Eisenbach, Yael; Gordon, Aaron; Sukhanov, Natalya; Peles, Elior

    2016-07-01

    Primary cultures of mixed neuron and Schwann cells prepared from dorsal root ganglia (DRG) are extensively used as a model to study myelination. These dissociated DRG cultures have the particular advantage of bypassing the difficulty in purifying mouse Schwann cells, which is often required when using mutant mice. However, the drawback of this experimental system is that it yields low amounts of myelin. Here we report a simple and efficient method to enhance myelination in vitro. We show that the addition of heparin or low molecular weight heparin to mixed DRG cultures markedly increases Schwann cells myelination. The myelin promoting activity of heparin results from specific inhibition of the soluble immunoglobulin (Ig)-containing isoforms of neuregulin 1 (i.e., NRG1 types I and II) that negatively regulates myelination. Heparin supplement provides a robust and reproducible method to increase myelination in a simple and commonly used culture system. GLIA 2016;64:1227-1234. PMID:27143444

  10. Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt;

    2015-01-01

    OBJECTIVE: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic...... myopathy. METHODS: We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance....../kg/min (p = 0.024). Fructose ingestion improved exercise tolerance in the patients. CONCLUSION: Similar to patients with McArdle disease, in whom muscle glycogenolysis is also impaired, GSDIIIa is associated with a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid...

  11. Protein misfolding as an underlying molecular defect in mucopolysaccharidosis III type C.

    Directory of Open Access Journals (Sweden)

    Matthew Feldhammer

    Full Text Available Mucopolysaccharidosis type IIIC or Sanfilippo syndrome type C (MPS IIIC, MIM #252930 is an autosomal recessive disorder caused by deficiency of the lysosomal membrane enzyme, heparan sulfate acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT, EC 2.3.1.78, which catalyses transmembrane acetylation of the terminal glucosamine residues of heparan sulfate prior to their hydrolysis by alpha-N-acetylglucosaminidase. Lysosomal storage of undegraded heparan sulfate in the cells of affected patients leads to neuronal death causing neurodegeneration and is accompanied by mild visceral and skeletal abnormalities, including coarse facies and joint stiffness. Surprisingly, the majority of MPS IIIC patients carrying missense mutations are as severely affected as those with splicing errors, frame shifts or nonsense mutations resulting in the complete absence of HGSNAT protein.In order to understand the effects of the missense mutations in HGSNAT on its enzymatic activity and biogenesis, we have expressed 21 mutant proteins in cultured human fibroblasts and COS-7 cells and studied their folding, targeting and activity. We found that 17 of the 21 missense mutations in HGSNAT caused misfolding of the enzyme, which is abnormally glycosylated and not targeted to the lysosome, but retained in the endoplasmic reticulum. The other 4 mutants represented rare polymorphisms which had no effect on the activity, processing and targeting of the enzyme. Treatment of patient cells with a competitive HGSNAT inhibitor, glucosamine, partially rescued several of the expressed mutants. Altogether our data provide an explanation for the severity of MPS IIIC and suggest that search for pharmaceutical chaperones can in the future result in therapeutic options for this disease.

  12. IFU spectroscopy of 10 early-type galactic nuclei - III. Properties of the circumnuclear gas emission

    Science.gov (United States)

    Ricci, T. V.; Steiner, J. E.; Menezes, R. B.

    2015-08-01

    Many early-type galaxies have ionized gas emission in their centres that extends to scales of ˜1 kpc. The majority of such objects are classified as low-ionization nuclear emission regions (LINERs), but the nature of their ionizing source is still not clear. The kinematics associated with these gaseous structures usually shows deviations from a pure rotational motion due to non-gravitational effects (e.g. outflows) or to non-axisymmetric potentials (e.g. bars or tri-axial systems). This is the third of a series of papers that describes a sample of 10 nearby (d 200 km s-1) early-type galaxies observed with the Gemini Multi-Object Spectrograph in Integral Field mode installed on the Gemini-South telescope. In Paper II, we performed spectral synthesis to subtract the stellar components from the data cubes of the sample galaxies in order to study their nuclear spectra. In this work, we analyse the circumnuclear gas emission (scales of ˜100 pc) of the sample galaxies and we compare the results with those obtained with Principal Component Analysis Tomography in Paper I. We detected circumnuclear gas emission in seven galaxies of the sample, all of them classified as LINERs. Pure gaseous discs are found in three galaxies. In two objects, gaseous discs are probably present, but their kinematics are affected by non-Keplerian motions. In one galaxy (IC 5181), we detected a spiral structure of gas that may be caused either by a non-axisymmetric potential or by an outflow together with a gaseous disc. In NGC 3136, an ionization bicone is present in addition to five compact structures with LINER-like emission. In galaxies with a gaseous disc, we found that ionizing photons emitted by an active galactic nucleus are not enough to explain the observed Hα flux along this structure. On the other hand, the Hα flux distribution and equivalent width along the direction perpendicular the gaseous disc suggest the presence of low-velocity ionized gas emission which seem to be related

  13. [Effectiveness of phytotherapy in supportive treatment of type 2 diabetes mellitus III. Momordica (Momordica charantia)].

    Science.gov (United States)

    Rudá-Kučerová, Jana; Kotolová, Hana; Koupý, David

    2015-09-01

    Momordica charantia is a thermophilic voluble plant from the tropical and subtropical regions of Asia, Africa and the Caribbean. In central Europe, momordica requires greenhouse plantations. Mature fruits resemble a cucumber or a pumpkin and can be used as other similar vegetables. Crude fruits are very bitter and refreshing. For centuries the plant has been known in Chinese traditional medicine for its antidiabetic effects as well as for the treatment of cancer or infections caused by worms, viruses and malaria. Antidiabetic effects are attributed namely to cucurbitane type triterpenoids, charantin, p-insulin and 9cis-11trans-13trans-conjugated linolenic acid. These substances in momordica preparations show antidiabetic effectiveness in clinical studies by increasing insulin secretion and deceasing insulin resistance or glucose absorption from the gut. Beside this main effect the extract possesses certain neuroprotective and antioxidant effects (especially p9cis-11trans-13trans-conjugated linolenic acid) and contributes to normalize blood lipid and adipokine levels which results in the normalization of metabolic syndrome. Antidiabetic effectiveness of momordica was compared to active treatment with several oral antidiabetic drugs and proved comparable effects. However, the number of studies is limited and their methodological approach variable. Therefore, the evidence is so far inconclusive.

  14. Synthesis, Structural Characterization, and Chiroptical Studies of Bidentate Salen-Type Lanthanide (III) Complexes.

    Science.gov (United States)

    Berardozzi, Roberto; Pescitelli, Gennaro; Di Pietro, Sebastiano; Resta, Claudio; Ballistreri, Francesco P; Pappalardo, Andrea; Tomaselli, Gaetano A; Di Bari, Lorenzo

    2015-12-01

    The salen-type ligand prepared with (R,R) diphenylethan-1,2-diamine and salicylaldehyde provides stable and inert complexes KLnL2 upon simple reaction with lanthanide halides or pseudohalides LnX3 (Ln = Tb(3+) -Lu(3+) ; X = Cl(-) or TfO(-) ) of its potassium salt. All the complexes were completely characterized through nuclear magnetic resonance (NMR), electronic circular dichroism (ECD) in the UV and some (Er(3+) , Tm(3+) , Yb(3+) ) also with Near-IR ECD (NIR-ECD) and luminescence (Tb(3+) , Tm(3+) ). Careful analysis of the NMR shifts demonstrated that the complexes are isostructural in solution and afforded an accurate geometry. This was further confirmed by means of Density Functional Theory (DFT) optimization of the Lu(3+) complex, and by comparing the ligand-centered experimental and time-dependent TD-DFT computed UV-ECD spectra. As final validation, we used the NIR-ECD spectrum of the Yb(3+) derivative calculated by means of Richardson's equations. The excellent match between calculated and experimental ECD spectra confirm the quality of the NMR structure. PMID:26422601

  15. IFU spectroscopy of 10 early-type galactic nuclei - III. Properties of the circumnuclear gas emission

    CERN Document Server

    Ricci, T V; Menezes, R B

    2015-01-01

    Many Early-type galaxies (ETG) have ionized gas emission in their centres that extends to scales of ~ 1kpc. The majority of such objects are classified as LINERs, but the nature of their ionizing source is still not clear. The kinematics associated with these gaseous structures usually shows deviations from a pure rotational motion due to non-gravitational effects or to non-axisymmetric potentials. This is the third of a series of papers that describes a sample of 10 nearby and massive ETG observed with the Gemini Multi-Object Spectrograph in Integral Field mode installed on the Gemini-South telescope. In paper II, we performed spectral synthesis to subtract the stellar components from the data cubes of the sample galaxies in order to study their nuclear spectra. Here, we analyse the circumnuclear gas emission (scales of ~ 100 pc) of the sample galaxies. Circumnuclear gas emission was detected in seven galaxies, all of them classified as LINERs. Pure gaseous discs are found in three galaxies. In two objects, ...

  16. [Effectiveness of phytotherapy in supportive treatment of type 2 diabetes mellitus III. Momordica (Momordica charantia)].

    Science.gov (United States)

    Rudá-Kučerová, Jana; Kotolová, Hana; Koupý, David

    2015-09-01

    Momordica charantia is a thermophilic voluble plant from the tropical and subtropical regions of Asia, Africa and the Caribbean. In central Europe, momordica requires greenhouse plantations. Mature fruits resemble a cucumber or a pumpkin and can be used as other similar vegetables. Crude fruits are very bitter and refreshing. For centuries the plant has been known in Chinese traditional medicine for its antidiabetic effects as well as for the treatment of cancer or infections caused by worms, viruses and malaria. Antidiabetic effects are attributed namely to cucurbitane type triterpenoids, charantin, p-insulin and 9cis-11trans-13trans-conjugated linolenic acid. These substances in momordica preparations show antidiabetic effectiveness in clinical studies by increasing insulin secretion and deceasing insulin resistance or glucose absorption from the gut. Beside this main effect the extract possesses certain neuroprotective and antioxidant effects (especially p9cis-11trans-13trans-conjugated linolenic acid) and contributes to normalize blood lipid and adipokine levels which results in the normalization of metabolic syndrome. Antidiabetic effectiveness of momordica was compared to active treatment with several oral antidiabetic drugs and proved comparable effects. However, the number of studies is limited and their methodological approach variable. Therefore, the evidence is so far inconclusive. PMID:26459126

  17. Photon storage in Lambda-type optically dense atomic media. III. Effects of inhomogeneous broadening

    CERN Document Server

    Gorshkov, A V; Lukin, M D; Sørensen, A S; Andre, Axel; Gorshkov, Alexey V.; Lukin, Mikhail D.; Sorensen, Anders S.

    2006-01-01

    In a recent paper [A.V. Gorshkov et al., e-print quant-ph/0604037 (2006)] and in the two preceding papers [A.V. Gorshkov et al., e-print quant-ph/0612082 (2006); e-print quant-ph/0612083 (2006)], we used a universal physical picture to optimize and demonstrate equivalence between a wide range of techniques for storage and retrieval of photon wave packets in homogeneously broadened Lambda-type atomic media, including the adiabatic reduction of the photon group velocity, pulse-propagation control via off-resonant Raman techniques, and photon-echo based techniques. In the present paper, we generalize this treatment to include inhomogeneous broadening both in atomic vapors and in solid state systems. In particular, we show that for the case of Doppler-broadened atoms, at high enough optical depth, all atoms contribute coherently to the storage process as if the medium were homogeneously broadened. Furthermore, we discuss the advantages and limitations of reversing the inhomogeneous broadening during the storage t...

  18. Quantitative proteomic analysis of Burkholderia pseudomallei Bsa type III secretion system effectors using hypersecreting mutants.

    Science.gov (United States)

    Vander Broek, Charles W; Chalmers, Kevin J; Stevens, Mark P; Stevens, Joanne M

    2015-04-01

    Burkholderia pseudomallei is an intracellular pathogen and the causative agent of melioidosis, a severe disease of humans and animals. One of the virulence factors critical for early stages of infection is the Burkholderia secretion apparatus (Bsa) Type 3 Secretion System (T3SS), a molecular syringe that injects bacterial proteins, called effectors, into eukaryotic cells where they subvert cellular functions to the benefit of the bacteria. Although the Bsa T3SS itself is known to be important for invasion, intracellular replication, and virulence, only a few genuine effector proteins have been identified and the complete repertoire of proteins secreted by the system has not yet been fully characterized. We constructed a mutant lacking bsaP, a homolog of the T3SS "gatekeeper" family of proteins that exert control over the timing and magnitude of effector protein secretion. Mutants lacking BsaP, or the T3SS translocon protein BipD, were observed to hypersecrete the known Bsa effector protein BopE, providing evidence of their role in post-translational control of the Bsa T3SS and representing key reagents for the identification of its secreted substrates. Isobaric Tags for Relative and Absolute Quantification (iTRAQ), a gel-free quantitative proteomics technique, was used to compare the secreted protein profiles of the Bsa T3SS hypersecreting mutants of B. pseudomallei with the isogenic parent strain and a bsaZ mutant incapable of effector protein secretion. Our study provides one of the most comprehensive core secretomes of B. pseudomallei described to date and identified 26 putative Bsa-dependent secreted proteins that may be considered candidate effectors. Two of these proteins, BprD and BapA, were validated as novel effector proteins secreted by the Bsa T3SS of B. pseudomallei.

  19. Search for heavy lepton partners of neutrinos in proton-proton collisions in the context of the type III seesaw mechanism

    CERN Document Server

    Chatrchyan, Serguei; Sirunyan, Albert M; Tumasyan, Armen; Adam, Wolfgang; Aguilo, Ernest; Bergauer, Thomas; Dragicevic, Marko; Erö, Janos; Fabjan, Christian; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hammer, Josef; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Kiesenhofer, Wolfgang; Knünz, Valentin; Krammer, Manfred; Krätschmer, Ilse; Liko, Dietrich; Mikulec, Ivan; Pernicka, Manfred; Rahbaran, Babak; Rohringer, Christine; Rohringer, Herbert; Schöfbeck, Robert; Strauss, Josef; Taurok, Anton; Waltenberger, Wolfgang; Walzel, Gerhard; Widl, Edmund; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Bansal, Monika; Bansal, Sunil; Cornelis, Tom; De Wolf, Eddi A; Janssen, Xavier; Luyckx, Sten; Mucibello, Luca; Ochesanu, Silvia; Roland, Benoit; Rougny, Romain; Selvaggi, Michele; Staykova, Zlatka; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Blekman, Freya; Blyweert, Stijn; D'Hondt, Jorgen; Gonzalez Suarez, Rebeca; Kalogeropoulos, Alexis; Maes, Michael; Olbrechts, Annik; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Villella, Ilaria; Clerbaux, Barbara; De Lentdecker, Gilles; Dero, Vincent; Gay, Arnaud; Hreus, Tomas; Léonard, Alexandre; Marage, Pierre Edouard; Mohammadi, Abdollah; Reis, Thomas; Thomas, Laurent; Vander Marcken, Gil; Vander Velde, Catherine; Vanlaer, Pascal; Wang, Jian; Adler, Volker; Beernaert, Kelly; Cimmino, Anna; Costantini, Silvia; Garcia, Guillaume; Grunewald, Martin; Klein, Benjamin; Lellouch, Jérémie; Marinov, Andrey; Mccartin, Joseph; Ocampo Rios, Alberto Andres; Ryckbosch, Dirk; Strobbe, Nadja; Thyssen, Filip; Tytgat, Michael; Verwilligen, Piet; Walsh, Sinead; Yazgan, Efe; Zaganidis, Nicolas; Basegmez, Suzan; Bruno, Giacomo; Castello, Roberto; Ceard, Ludivine; Delaere, Christophe; Du Pree, Tristan; Favart, Denis; Forthomme, Laurent; Giammanco, Andrea; Hollar, Jonathan; Lemaitre, Vincent; Liao, Junhui; Militaru, Otilia; Nuttens, Claude; Pagano, Davide; Pin, Arnaud; Piotrzkowski, Krzysztof; Schul, Nicolas; Vizan Garcia, Jesus Manuel; Beliy, Nikita; Caebergs, Thierry; Daubie, Evelyne; Hammad, Gregory Habib; Alves, Gilvan; Correa Martins Junior, Marcos; De Jesus Damiao, Dilson; Martins, Thiago; Pol, Maria Elena; Henrique Gomes E Souza, Moacyr; Aldá Júnior, Walter Luiz; Carvalho, Wagner; Custódio, Analu; Da Costa, Eliza Melo; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Matos Figueiredo, Diego; Mundim, Luiz; Nogima, Helio; Oguri, Vitor; Prado Da Silva, Wanda Lucia; Santoro, Alberto; Soares Jorge, Luana; Sznajder, Andre; Souza Dos Anjos, Tiago; Bernardes, Cesar Augusto; De Almeida Dias, Flavia; Tomei, Thiago; De Moraes Gregores, Eduardo; Lagana, Caio; Da Cunha Marinho, Franciole; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Genchev, Vladimir; Iaydjiev, Plamen; Piperov, Stefan; Rodozov, Mircho; Stoykova, Stefka; Sultanov, Georgi; Tcholakov, Vanio; Trayanov, Rumen; Vutova, Mariana; Dimitrov, Anton; Hadjiiska, Roumyana; Kozhuharov, Venelin; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Jiang, Chun-Hua; Liang, Dong; Liang, Song; Meng, Xiangwei; Tao, Junquan; Wang, Jian; Wang, Xianyou; Wang, Zheng; Xiao, Hong; Xu, Ming; Zang, Jingjing; Zhang, Zhen; Asawatangtrakuldee, Chayanit; Ban, Yong; Guo, Yifei; Li, Wenbo; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Teng, Haiyun; Wang, Dayong; Zhang, Linlin; Zou, Wei; Avila, Carlos; Gomez, Juan Pablo; Gomez Moreno, Bernardo; Osorio Oliveros, Andres Felipe; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Plestina, Roko; Polic, Dunja; Puljak, Ivica; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Duric, Senka; Kadija, Kreso; Luetic, Jelena; Morovic, Srecko; Attikis, Alexandros; Galanti, Mario; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Finger, Miroslav; Finger Jr, Michael; Assran, Yasser; Elgammal, Sherif; Ellithi Kamel, Ali; Khalil, Shaaban; Mahmoud, Mohammed; Radi, Amr; Kadastik, Mario; Müntel, Mait; Raidal, Martti; Rebane, Liis; Tiko, Andres; Eerola, Paula; Fedi, Giacomo; Voutilainen, Mikko; Härkönen, Jaakko; Heikkinen, Mika Aatos; Karimäki, Veikko; Kinnunen, Ritva; Kortelainen, Matti J; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Peltola, Timo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Ungaro, Donatella; Wendland, Lauri; Banzuzi, Kukka; Karjalainen, Ahti; Korpela, Arja; Tuuva, Tuure; Besancon, Marc; Choudhury, Somnath; Dejardin, Marc

    2012-01-01

    A search is presented in proton-proton collisions at $\\sqrt{s}$ = 7 TeV for fermionic triplet states expected in type III seesaw models. The search is performed using final states with three isolated charged leptons and an imbalance in transverse momentum. The data, collected with the CMS detector at the LHC, correspond to an integrated luminosity of 4.9 inverse femtobarns. No excess of events is observed above the background predicted by the standard model, and the results are interpreted in terms of limits on production cross sections and masses of the heavy partners of the neutrinos in type III seesaw models. Depending on the considered scenarios, lower limits are obtained on the mass of the heavy partner of the neutrino that range from 180 to 210 GeV. These are the first limits on the production of type III seesaw fermionic triplet states reported by an experiment at the LHC.

  20. The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters

    DEFF Research Database (Denmark)

    Nielsen, Mette J; Nedergaard, Anders F; Sun, Shu;

    2013-01-01

    AIM: The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3). METHODS: The monoclonal antibody...... was raised against the N-protease mediated cleavage site of the N-terminal propeptide of type III collagen and a competitive ELISA was developed using the selected antibody. The assay was evaluated in relation to neo-epitope specificity, technical performance, and as a marker for liver fibrosis and muscle...... mass using the rat carbon tetrachloride (CCl4) model and a study of immobilization induced muscle loss in humans, respectively. RESULTS: The ELISA was neo-epitope specific, technically stable and can be assessed in serum and plasma samples. In the CCl4 liver fibrosis model it was observed that serum...

  1. Myocardial repair with long-term and low-dose administration of a nitric oxide synthesis inhibitor. Myofibroblasts, type III collagen and fibronectin

    Directory of Open Access Journals (Sweden)

    Pessanha Mônica Gomes

    1999-01-01

    Full Text Available OBJECTIVE: To study the healing process of the myocardium in hypertensive rats undergoing inhibition of nitric oxide synthesis. METHODS: Two groups of animals were studied: one received L-NAME, 12mg/kg/day, and the other was a control group. The presence of type III collagen, fibronectin, and alpha-smooth muscle actin-positive cells was assessed by immunohistochemistry. RESULTS: Fibronectin was seen in both early and late lesions, while type III collagen was seen mainly in areas of incomplete healing, situated among myocytes and around the intramyocardial branches of the coronary arteries. Areas representing early and late lesions showed a population of spindle-shaped cells. Immunohistochemistry showed that these cells were positive for alpha-smooth muscle actin. CONCLUSION: In the myocardium of hypertensive rats, the alpha-smooth muscle actin-positive cells are related to the accumulation of type III collagen and fibronectin in the areas of myocardial damage.

  2. Novel compound heterozygous mutations in DYNC2H1 in a patient with severe short-rib polydactyly syndrome type III phenotype.

    Science.gov (United States)

    Okamoto, Toshio; Nagaya, Ken; Kawata, Yumi; Asai, Hiroko; Tsuchida, Etsushi; Nohara, Fumikatsu; Okajima, Kazuki; Azuma, Hiroshi

    2015-08-01

    Short-rib polydactyly syndrome type III is an autosomal recessive lethal skeletal ciliopathy, which is phenotypically similar to nonlethal asphyxiating thoracic dystrophy. Mutations in DYNC2H1 have been identified in both of these disorders, indicating that they are variants of a single disorder. However, short-rib polydactyly syndrome type III is the more severe variant. Here, we report novel compound heterozygous mutations in DYNC2H1 (p.E1894fsX10 and p.R3004C) in a patient with typical short-rib polydactyly syndrome type III phenotype. R3004 is located within the microtubule-binding domain of DYNC2H1, and its substitution is predicted to disrupt the interaction with microtubules. Considering the severe phenotype of our patient, our findings suggest that R3004 may be a key residue for the microtubule-binding affinity of dynein.

  3. Statistical Survey of Type III Radio Bursts at Long Wavelengths Observed by the Solar TErrestrial RElations Observatory (STEREO)/Waves Instruments: Goniopolarimetric Properties and Radio Source Locations

    CERN Document Server

    Krupar, Vratislav; Santolik, Ondrej; Cecconi, Baptiste; Kruparova, Oksana

    2014-01-01

    We have performed statistical analysis of a large number of Type III radio bursts observed by STEREO between May 2007 and February 2013. Only intense, simple, and isolated cases have been included in our data set. We have focused on the goniopolarimetric (GP, also referred to as direction-finding) properties at frequencies between $125$ kHz and $2$ MHz. The apparent source size $\\gamma$ is very extended ($\\approx60^\\circ$) for the lowest analyzed frequencies. Observed apparent source sizes $\\gamma$ expand linearly with a radial distance from the Sun at frequencies below $1$ MHz. We have shown that Type III radio bursts statistically propagate in the ecliptic plane. Calculated positions of radio sources suggest that scattering of the primary beam pattern plays an important role in the propagation of Type III radio bursts in the IP medium.

  4. Search for heavy lepton partners of neutrinos in proton-proton collisions in the context of the type III seesaw mechanism

    International Nuclear Information System (INIS)

    A search is presented in proton-proton collisions at √(s)=7 TeV for fermionic triplet states expected in type III seesaw models. The search is performed using final states with three isolated charged leptons and an imbalance in transverse momentum. The data, collected with the CMS detector at the LHC, correspond to an integrated luminosity of 4.9 fb-1. No excess of events is observed above the background predicted by the standard model, and the results are interpreted in terms of limits on production cross sections and masses of the heavy partners of the neutrinos in type III seesaw models. Depending on the considered scenarios, lower limits are obtained on the mass of the heavy partner of the neutrino that range from 180 to 210 GeV. These are the first limits on the production of type III seesaw fermionic triplet states reported by an experiment at the LHC.

  5. Search for heavy lepton partners of neutrinos in proton-proton collisions in the context of the type III seesaw mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Chatrchyan, S.; Khachatryan, V.; Sirunyan, A.M.; Tumasyan, A. [Yerevan Physics Institute, Yerevan (Armenia); Adam, W.; Aguilo, E.; Bergauer, T.; Dragicevic, M.; Eroe, J.; Fabjan, C.; Friedl, M.; Fruehwirth, R.; Ghete, V.M.; Hammer, J.; Hoermann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knuenz, V.; Krammer, M. [Institut fuer Hochenergiephysik der OeAW, Wien (Austria); and others

    2012-12-05

    A search is presented in proton-proton collisions at {radical}(s)=7 TeV for fermionic triplet states expected in type III seesaw models. The search is performed using final states with three isolated charged leptons and an imbalance in transverse momentum. The data, collected with the CMS detector at the LHC, correspond to an integrated luminosity of 4.9 fb{sup -1}. No excess of events is observed above the background predicted by the standard model, and the results are interpreted in terms of limits on production cross sections and masses of the heavy partners of the neutrinos in type III seesaw models. Depending on the considered scenarios, lower limits are obtained on the mass of the heavy partner of the neutrino that range from 180 to 210 GeV. These are the first limits on the production of type III seesaw fermionic triplet states reported by an experiment at the LHC.

  6. Outcomes of Patients With Acute Type B (DeBakey III) Aortic Dissection

    Science.gov (United States)

    Afifi, Rana O.; Sandhu, Harleen K.; Leake, Samuel S.; Boutrous, Mina L.; Kumar, Varsha; Azizzadeh, Ali; Charlton-Ouw, Kristofer M.; Saqib, Naveed U.; Nguyen, Tom C.; Miller, Charles C.; Safi, Hazim J.

    2015-01-01

    Background— Aortic dissection remains the most common aortic catastrophe. In the endovascular era, the management of acute type B aortic dissection (ATBAD) is undergoing dramatic changes. The aim of this study is to evaluate the long-term outcomes of patients with ATBAD who were treated at our center over a 13-year period. Methods and Results— We reviewed patients with ATBAD between 2001 and 2014, analyzing variables based on status (complicated [c] versus uncomplicated [u]) and treatment modalities. We defined cATBAD as rupture, expansion of diameter on imaging during the admission, persistent pain, or clinical malperfusion leading to a deficit in cerebral, spinal, visceral, renal, or peripheral vascular territories at presentation or during initial hospitalization. Postoperative outcomes were defined as deficits not present before the intervention. Outcomes were compared between the groups by use of Kaplan-Meier and descriptive statistics. We treated 442 patients with ATBAD. Of those 442, 60.6% had uATBAD and were treated medically, and 39.4% had cATBAD, of whom 39.0% were treated medically to 30.0% with open repair, 21.3% with thoracic endovascular aortic repair, and 9.7% with other open peripheral procedures. Intervention-free survival at 1 and 5 years was 84.8% and 62.7% for uATBAD, 61.8% and 44.0% for cATBAD-medical, 69.2% and 47.2% for cATBAD-open, and 68.0% and 42.5% for cATBAD–thoracic endovascular aortic repair, respectively (P=0.001). Overall survival was significantly related primarily to complicated presentation. Conclusions— In our experience, early and late outcomes of ATBAD were dependent on the presence of complications, with cATBAD faring worse. Although uATBAD was associated with favorable early survival, late complications still occurred, mandating radiographic surveillance and open or endovascular interventions. Prospective trials are required to better determine the optimal therapy for uATBAD. PMID:26304666

  7. Protection of epithelial cells from Salmonella enterica serovar Enteritidis invasion by antibodies against the SPI-1 type III secretion system.

    Science.gov (United States)

    Desin, Taseen S; Mickael, Claudia S; Lam, Po-King S; Potter, Andrew A; Köster, Wolfgang

    2010-06-01

    Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) is one of the major causes of bacterial food-borne illness in humans. During the course of infection, Salmonella Enteritidis uses 2 type III secretion systems (T3SS), one of which is encoded on Salmonella pathogenicity island 1 (SPI-1). SPI-1 plays a major role in the invasion process. In the present study, we evaluated the effect of sera against the SPI-1 T3SS components on invasion in vitro using polarized human intestinal epithelial cells (Caco-2). Antisera to SipD protected Caco-2 cells against entry of wild-type Salmonella Enteritidis. On the other hand, sera against InvG, PrgI, SipA, SipC, SopB, SopE, and SopE2 did not affect Salmonella Enteritidis entry. To illustrate the specificity of anti-SipD mediated inhibition, SipD-specific antibodies were depleted from the serum. Antiserum depleted of SipD-specific antibodies lost its capacity to inhibit Salmonella Enteritidis entry. Thus, we demonstrate for the first time that antibodies against the SPI-1 needle tip protein (SipD) inhibit Salmonella Enteritidis invasion and that the SipD protein may be an important target in blocking SPI-1 mediated virulence of Salmonella Enteritidis.

  8. Type III_1 equilibrium states of the Toeplitz algebra of the affine semigroup over the natural numbers

    CERN Document Server

    Laca, Marcelo

    2010-01-01

    We complete the analysis of KMS-states of the Toeplitz algebra of the affine semigroup over the natural numbers, recently studied by Raeburn and the first author, by showing that for every inverse temperature beta in the critical interval [1,2], the unique KMS_beta-state is of type III_1. We prove this by reducing the type classification from the Toeplitz algebra to that of the symmetric part of the Bost-Connes system, with a shift in inverse temperature. To carry out this reduction we first obtain a parametrization of the Nica spectrum of the Toeplitz algebra in terms of an adelic space. Combining a characterization of traces on crossed products due to the second author with an analysis of the action of the affine semigroup on the Nica spectrum, we can also recover all the KMS-states originally computed by Raeburn and the first author. Our computation sheds light on why there is a free transitive circle action on the extremal KMS_beta-states for beta>2 that does not ostensibly come from an action on the C*-a...

  9. Asymptotic behavior of the solution to the Cauchy problem for the Timoshenko system in thermoelasticity of type III

    KAUST Repository

    Rahali, Radouane

    2013-03-01

    In this paper, we investigate the decay property of a Timoshenko system in thermoelasticity of type III in the whole space where the heat conduction is given by the Green and Naghdi theory. Surprisingly, we show that the coupling of the Timoshenko system with the heat conduction of Green and Naghdi\\'s theory slows down the decay of the solution. In fact we show that the L-2-norm of the solution decays like (1 + t)(-1/8), while in the case of the coupling of the Timoshenko system with the Fourier or Cattaneo heat conduction, the decay rate is of the form (1 + t)(-1/4) [25]. We point out that the decay rate of (1 + t)(-1/8) has been obtained provided that the initial data are in L-1 (R) boolean AND H-s (R); (s >= 2). If the wave speeds of the fi rst two equations are di ff erent, then the decay rate of the solution is of regularity-loss type, that is in this case the previous decay rate can be obtained only under an additional regularity assumption on the initial data. In addition, by restricting the initial data to be in H-s (R) boolean AND L-1,L-gamma (R) with gamma is an element of [0; 1], we can derive faster decay estimates with the decay rate improvement by a factor of t(-gamma/4).

  10. The GAP Portion of Pseudomonas Aeruginosa Type III Secreted Toxin ExoS Upregulates Total and Surface Levels of Wild Type CFTR

    Directory of Open Access Journals (Sweden)

    Deepali N. Tukaye

    2013-02-01

    Full Text Available Background: Pseudomonas aeruginosa (PA infections account for a large percentage of fatal hospital acquired pneumonias. One of the PA Type III secreted toxin (TTST ExoS, a bifunctional protein with N-terminal GTPase activating protein (GAP and C-terminal ADP rybosyl transferase (ADPRT activities, significantly contributes to PA virulence by targeting small molecular weight G-proteins (SMWGP. In this study, we have looked at one of the mechanisms by which the GAP portion of ExoS (ExoS-GAP mediates cellular toxicity. Methods: The effects of ExoS-GAP on CFTR trafficking were studied in CFBE41o- Kir 2.2 and MDCK cell lines stably expressing CFTR using a transient transfection system. Results: Transient transfection of ExoS-GAP increased the total and surface protein levels of mature wild type CFTR in epithelial cells stably expressing wild type (WT CFTR. The effect of ExoS-GAP was specific to CFTR in bronchial epithelial cells since it did not affect the total protein levels of Na+/K+ATPase, another membrane protein. A point mutation in the ExoS GAP domain (R146K, known to disrupt its catalytic GAP activity, abolished the effect of ExoS-GAP on WT CFTR. Lysosomal inhibition studies with Bafilomycin A1 indicate that ExoS-GAP decreased lysosomal degradation of the mature WT CFTR with concomitant increase in the total levels of mature WT CFTR. However, ExoS-GAP did not increase the total protein levels of ∆F508CFTR. Conclusion: The GAP portion of the PA TTST ExoS increases the total and surface levels of wild type CFTR in vitro mammalian cell system. The effect of ExoS-GAP on WT CFTR total protein levels provides new insight into understanding the virulent pathophysiology of PA infections.

  11. Crystal structure of Legionella DotD: insights into the relationship between type IVB and type II/III secretion systems.

    Directory of Open Access Journals (Sweden)

    Noboru Nakano

    Full Text Available The Dot/Icm type IVB secretion system (T4BSS is a pivotal determinant of Legionella pneumophila pathogenesis. L. pneumophila translocate more than 100 effector proteins into host cytoplasm using Dot/Icm T4BSS, modulating host cellular functions to establish a replicative niche within host cells. The T4BSS core complex spanning the inner and outer membranes is thought to be made up of at least five proteins: DotC, DotD, DotF, DotG and DotH. DotH is the outer membrane protein; its targeting depends on lipoproteins DotC and DotD. However, the core complex structure and assembly mechanism are still unknown. Here, we report the crystal structure of DotD at 2.0 Å resolution. The structure of DotD is distinct from that of VirB7, the outer membrane lipoprotein of the type IVA secretion system. In contrast, the C-terminal domain of DotD is remarkably similar to the N-terminal subdomain of secretins, the integral outer membrane proteins that form substrate conduits for the type II and the type III secretion systems (T2SS and T3SS. A short β-segment in the otherwise disordered N-terminal region, located on the hydrophobic cleft of the C-terminal domain, is essential for outer membrane targeting of DotH and Dot/Icm T4BSS core complex formation. These findings uncover an intriguing link between T4BSS and T2SS/T3SS.

  12. Change in muscle strength over time in spinal muscular atrophy types II and III. A long-term follow-up study

    DEFF Research Database (Denmark)

    Werlauff, U; Vissing, J; Steffensen, B F

    2012-01-01

    Whether muscle strength deteriorates with time in spinal muscular atrophy (SMA) types II and III is still debated. We present a long-term follow-up study on muscle strength in 30 patients with SMA types II and III. Median follow-up time was 17 years. Median number of assessments was four. All pat...... patients were assessed by Manual Muscle Testing (MMT), Brooke upper limb scale and EK scale. There was a difference in muscle strength of the upper limbs from first to last assessment in SMA II (p...

  13. Significant type I and type III collagen production from human periodontal ligament fibroblasts in 3D peptide scaffolds without extra growth factors.

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Kumada

    Full Text Available We here report the development of two peptide scaffolds designed for periodontal ligament fibroblasts. The scaffolds consist of one of the pure self-assembling peptide scaffolds RADA16 through direct coupling to short biologically active motifs. The motifs are 2-unit RGD binding sequence PRG (PRGDSGYRGDS and laminin cell adhesion motif PDS (PDSGR. RGD and laminin have been previously shown to promote specific biological activities including periodontal ligament fibroblasts adhesion, proliferation and protein production. Compared to the pure RADA16 peptide scaffold, we here show that these designer peptide scaffolds significantly promote human periodontal ligament fibroblasts to proliferate and migrate into the scaffolds (for approximately 300 microm/two weeks. Moreover these peptide scaffolds significantly stimulated periodontal ligament fibroblasts to produce extracellular matrix proteins without using extra additional growth factors. Immunofluorescent images clearly demonstrated that the peptide scaffolds were almost completely covered with type I and type III collagens which were main protein components of periodontal ligament. Our results suggest that these designer self-assembling peptide nanofiber scaffolds may be useful for promoting wound healing and especially periodontal ligament tissue regeneration.

  14. Involvement of RNA2-encoded proteins in the specific transmission of Grapevine fanleaf virus by its nematode vector Xiphinema index.

    Science.gov (United States)

    Belin, C; Schmitt, C; Demangeat, G; Komar, V; Pinck, L; Fuchs, M

    2001-12-01

    The nepovirus Grapevine fanleaf virus (GFLV) is specifically transmitted by the nematode Xiphinema index. To identify the RNA2-encoded proteins involved in X. index-mediated spread of GFLV, chimeric RNA2 constructs were engineered by replacing the 2A, 2B(MP), and/or 2C(CP) sequences of GFLV with their counterparts in Arabis mosaic virus (ArMV), a closely related nepovirus which is transmitted by Xiphinema diversicaudatum but not by X. index. Among the recombinant viruses obtained from transcripts of GFLV RNA1 and chimeric RNA2, only those which contained the 2C(CP) gene (504 aa) and 2B(MP) contiguous 9 C-terminal residues of GFLV were transmitted by X. index as efficiently as natural and synthetic wild-type GFLV, regardless of the origin of the 2A and 2B(MP) genes. As expected, ArMV was not transmitted probably because it is not retained by X. index. These results indicate that the determinants responsible for the specific spread of GFLV by X. index are located within the 513 C-terminal residues of the polyprotein encoded by RNA2.

  15. Combinative effects of a bacterial type-III effector and a biocontrol bacterium on rice growth and disease resistance

    Indian Academy of Sciences (India)

    Haiying Ren; Ganyu Gu; Juying Long; Qian Yin; Tingquan Wu; Tao Song; Shujian Zhang; Zhiyi Chen; Hansong Dong

    2006-12-01

    Expression of HpaGXoo, a bacterial type-III effector, in transgenic plants induces disease resistance. Resistance also can be elicited by biocontrol bacteria. In both cases, plant growth is often promoted. Here we address whether biocontrol bacteria and HpaGXoo can act together to provide better results in crop improvement. We studied effects of Pseudomonas cepacia on the rice variety R109 and the hpaGXoo-expressing rice line HER1. Compared to R109, HER1 showed increased growth, grain yield, and defense responses toward diseases and salinity stress. Colonization of roots by P. cepacia caused 20% and 13% increase, in contrast to controls, in root growth of R109 and HER1. Growth of leaves and stems also increased in R109 but that of HER1 was inhibited. When P. cepacia colonization was subsequent to plant inoculation with Rhizoctonia solani, a pathogen that causes sheath blight, the disease was less severe than controls in both R109 and HER1; HER1, nevertheless, was more resistant, suggesting that P. cepacia and HpaGXoo cooperate in inducing disease resistance. Several genes that critically regulate growth and defense behaved differentially in HER1 and R109 while responding to P. cepacia. In R109 leaves, the OsARF1 gene, which regulates plant growth, was expressed in consistence with growth promotion by P. cepacia. Inversely, OsARF1 expression was coincident with inhibition in growth of HER1 leaves. In both plants, the expression of OsEXP1, which encodes an expansin protein involved in plant growth, was concomitant with growth promotion in leaves instead of roots, in response to P. cepacia. We also studied OsMAPK, a gene that encodes a mitogen-activated protein kinase and controls defense responses toward salinity and infection by pathogens in rice. In response to P. cepacia, an early expression of OsMAPK was coincident with R109 resistance to the disease, while HER1 expressed the gene similarly whether P. cepacia was present or not. Evidently, P. cepacia and GXoo

  16. Evaluation of W/P Ratio, Setting Time and Compressive Strength of Dental Stone Type III and IV Marketed in Jakarta

    Directory of Open Access Journals (Sweden)

    Yosi Kusuma Eriwati

    2015-10-01

    Full Text Available Dental gypsum products in Indonesia are mainly imported from countries with non-tropical weather. Mostly, these gypsum products marketed in Jakarta are without adequate packaging, data or manipulative and maintenance instructions, which can cause misuse & abuse in the materials manipulation and handling. The purpose of this study was to evaluate the W/P ratio, setting time and compressive strength of dental stone type III and IV in relation with room temperature condition and relative humidity in Jakarta, Indonesia. One hundred and eighty dental stone Type III (unlabelled Blue Hard Stone; Giludur, Germany: Moldaroc, Germany and Type IV (New Fujirock, Japan; Glastone, USA; unlabelled Quickstone specimens were made as recommended by ISO 6873-1983 for setting time (with Vicat needle and compressive strength determination (Shimadzu mechanical testing machine with W/P ratio variables of 0.28; 0.29; 0.30 for Type III and 0.20; 0.21; 0.22 for type IV. The tests were conducted in 2 rooms with different temperature and humidity and with and without air-conditioned. Statistical analysis using T-test. The results shows that the increasing of W/P ratio will decrease the dental stone type III and IV setting time. Jakarta condition of high room temperature and relative humidity significantly shorten the setting time of Moldaroc and New Fujirock. The rest of the stones were reduced statistically insignificant. It can be concluded that the temperature and humidity in Jakarta can influence the setting time and compressive strength of dental stone type III and IV. However, since the setting time and strength values are still within the ISO standard, these stones can be accepted and used in Indonesia.

  17. NMR characterization of the interaction of the Salmonella type III secretion system protein SipD and bile salts.

    Science.gov (United States)

    Wang, Yu; Nordhues, Bryce A; Zhong, Dalian; De Guzman, Roberto N

    2010-05-18

    Salmonella and Shigella bacteria require the type III secretion system (T3SS) to inject virulence proteins into their hosts and initiate infections. The tip proteins SipD and IpaD are critical components of the Salmonella and Shigella T3SS, respectively. Recently, SipD and IpaD have been shown to interact with bile salts, which are enriched in the intestines, and are hypothesized to act as environmental sensors for these enteric pathogens. Bile salts activate the Shigella T3SS but repress the Salmonella T3SS, and the mechanism of this differing response to bile salts is poorly understood. Further, how SipD binds to bile salts is currently unknown. Computer modeling predicted that IpaD binds the bile salt deoxycholate in a cleft formed by the N-terminal domain and the long central coiled coil of IpaD. Here, we used NMR methods to determine which SipD residues are affected by the interaction with the bile salts deoxycholate, chenodeoxycholate, and taurodeoxcholate. The bile salts perturbed nearly the same set of SipD residues; however, the largest chemical shift perturbations occurred away from what was predicted for the bile salt binding site in IpaD. Our NMR results indicate that that bile salt interaction of SipD will be different from what was predicted for IpaD, suggesting a possible mechanism for the differing response of Salmonella and Shigella to bile salts.

  18. A global role for Fis in the transcriptional control of metabolism and type III secretion in Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Kelly, Arlene; Goldberg, Martin D; Carroll, Ronan K; Danino, Vittoria; Hinton, Jay C D; Dorman, Charles J

    2004-07-01

    Fis is a key DNA-binding protein involved in nucleoid organization and modulation of many DNA transactions, including transcription in enteric bacteria. The regulon of genes whose expression is influenced by Fis in Salmonella enterica serovar Typhimurium (S. typhimurium) has been defined by DNA microarray analysis. These data suggest that Fis plays a central role in coordinating the expression of both metabolic and type III secretion factors. The genes that were most strongly up-regulated by Fis were those involved in virulence and located in the pathogenicity islands SPI-1, SPI-2, SPI-3 and SPI-5. Similarly, motility and flagellar genes required Fis for full expression. This was shown to be a direct effect as purified Fis protein bound to the promoter regions of representative flagella and SPI-2 genes. Genes contributing to aspects of metabolism known to assist the bacterium during survival in the mammalian gut were also Fis-regulated, usually negatively. This category included components of metabolic pathways for propanediol utilization, biotin synthesis, vitamin B(12) transport, fatty acids and acetate metabolism, as well as genes for the glyoxylate bypass of the tricarboxylic acid cycle. Genes found to be positively regulated by Fis included those for ethanolamine utilization. The data reported reveal the central role played by Fis in coordinating the expression of both housekeeping and virulence factors required by S. typhimurium during life in the gut lumen or during systemic infection of host cells.

  19. Cholesterol binding by the bacterial type III translocon is essential for virulence effector delivery into mammalian cells.

    Science.gov (United States)

    Hayward, Richard D; Cain, Robert J; McGhie, Emma J; Phillips, Neil; Garner, Matthew J; Koronakis, Vassilis

    2005-05-01

    A ubiquitous early step in infection of man and animals by enteric bacterial pathogens like Salmonella, Shigella and enteropathogenic Escherichia coli (EPEC) is the translocation of virulence effector proteins into mammalian cells via specialized type III secretion systems (TTSSs). Translocated effectors subvert the host cytoskeleton and stimulate signalling to promote bacterial internalization or survival. Target cell plasma membrane cholesterol is central to pathogen-host cross-talk, but the precise nature of its critical contribution remains unknown. Using in vitro cholesterol-binding assays, we demonstrate that Salmonella (SipB) and Shigella (IpaB) TTSS translocon components bind cholesterol with high affinity. Direct visualization of cell-associated fluorescently labelled SipB and parallel immunogold transmission electron microscopy revealed that cholesterol levels limit both the amount and distribution of plasma membrane-integrated translocon. Correspondingly, cholesterol depletion blocked effector translocation into cultured mammalian cells by not only the related Salmonella and Shigella TTSSs, but also the more divergent EPEC system. The data reveal that cholesterol-dependent association of the bacterial TTSS translocon with the target cell plasma membrane is essential for translocon activation and effector delivery into mammalian cells.

  20. Transcriptional profiling of Bordetella pertussis reveals requirement of RNA chaperone Hfq for Type III secretion system functionality.

    Science.gov (United States)

    Bibova, Ilona; Hot, David; Keidel, Kristina; Amman, Fabian; Slupek, Stephanie; Cerny, Ondrej; Gross, Roy; Vecerek, Branislav

    2015-01-01

    Bordetella pertussis, the causative agent of human whooping cough (pertussis) produces a complex array of virulence factors in order to establish efficient infection in the host. The RNA chaperone Hfq and small regulatory RNAs are key players in posttranscriptional regulation in bacteria and have been shown to play an essential role in virulence of a broad spectrum of bacterial pathogens. This study represents the first attempt to characterize the Hfq regulon of the human pathogen B. pertussis under laboratory conditions as well as upon passage in the host and indicates that loss of Hfq has a profound effect on gene expression in B. pertussis. Comparative transcriptional profiling revealed that Hfq is required for expression of several virulence factors in B. pertussis cells including the Type III secretion system (T3SS). In striking contrast to the wt strain, T3SS did not become operational in the hfq mutant passaged either through mice or macrophages thereby proving that Hfq is required for the functionality of the B. pertussis T3SS. Likewise, expression of virulence factors vag8 and tcfA encoding autotransporter and tracheal colonization factor, respectively, was strongly reduced in the hfq mutant. Importantly, for the first time we demonstrate that B. pertussis T3SS can be activated upon contact with macrophage cells in vitro.

  1. Decreased abundance of type III secretion system-inducing signals in Arabidopsis mkp1 enhances resistance against Pseudomonas syringae

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Jeffrey C.; Wan, Ying; Kim, Young-Mo; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Peck, Scott C.

    2014-04-21

    Many phytopathogenic bacteria use a type III secretion system (T3SS) to inject defense-suppressing effector proteins into host cells. Genes encoding the T3SS are induced at the start of infection, yet host signals that initiate T3SS gene expression are poorly understood. Here we identify several plant-derived metabolites that induce the T3SS in the bacterial pathogen Pseudomonas syringae pv tomato DC3000. In addition, we report that mkp1 (mapk phosphatase 1), an Arabidopsis mutant that is more resistant to bacterial infection, produces decreased levels of these T3SS-inducing metabolites. Consistent with the observed decrease in these metabolites, T3SS effector delivery by DC3000 was impaired in mkp1. Addition of the bioactive metabolites to the mkp1-DC3000 interaction fully restored T3SS effector delivery and suppressed enhanced resistance in mkp1. Together, these results demonstrate that DC3000 perceives multiple signals derived from plants to initiate their virulence program, and reveal a new layer of molecular communication between plants and these pathogenic bacteria.

  2. BEAN 2.0: an integrated web resource for the identification and functional analysis of type III secreted effectors.

    Science.gov (United States)

    Dong, Xiaobao; Lu, Xiaotian; Zhang, Ziding

    2015-01-01

    Gram-negative pathogenic bacteria inject type III secreted effectors (T3SEs) into host cells to sabotage their immune signaling networks. Because T3SEs constitute a meeting-point of pathogen virulence and host defense, they are of keen interest to host-pathogen interaction research community. To accelerate the identification and functional understanding of T3SEs, we present BEAN 2.0 as an integrated web resource to predict, analyse and store T3SEs. BEAN 2.0 includes three major components. First, it provides an accurate T3SE predictor based on a hybrid approach. Using independent testing data, we show that BEAN 2.0 achieves a sensitivity of 86.05% and a specificity of 100%. Second, it integrates a set of online sequence analysis tools. Users can further perform functional analysis of putative T3SEs in a seamless way, such as subcellular location prediction, functional domain scan and disorder region annotation. Third, it compiles a database covering 1215 experimentally verified T3SEs and constructs two T3SE-related networks that can be used to explore the relationships among T3SEs. Taken together, by presenting a one-stop T3SE bioinformatics resource, we hope BEAN 2.0 can promote comprehensive understanding of the function and evolution of T3SEs.

  3. Inhibition of a type III secretion system by the deletion of a short loop in one of its membrane proteins.

    Science.gov (United States)

    Meshcheryakov, Vladimir A; Kitao, Akio; Matsunami, Hideyuki; Samatey, Fadel A

    2013-05-01

    The membrane protein FlhB is a highly conserved component of the flagellar secretion system. It is composed of an N-terminal transmembrane domain and a C-terminal cytoplasmic domain (FlhBC). Here, the crystal structures of FlhBC from Salmonella typhimurium and Aquifex aeolicus are described at 2.45 and 2.55 Å resolution, respectively. These flagellar FlhBC structures are similar to those of paralogues from the needle type III secretion system, with the major difference being in a linker that connects the transmembrane and cytoplasmic domains of FlhB. It was found that deletion of a short flexible loop in a globular part of Salmonella FlhBC leads to complete inhibition of secretion by the flagellar secretion system. Molecular-dynamics calculations demonstrate that the linker region is the most flexible part of FlhBC and that the deletion of the loop reduces this flexibility. These results are in good agreement with previous studies showing the importance of the linker in the function of FlhB and provide new insight into the relationship between the different parts of the FlhBC molecule. PMID:23633590

  4. A novel transcriptional autoregulatory loop enhances expression of the Pantoea stewartii subsp. stewartii Hrp type III secretion system.

    Science.gov (United States)

    Merighi, Massimo; Majerczak, Doris R; Coplin, David L

    2005-02-15

    The hrp type III secretion regulon of Pantoea stewartii is regulated by a cascade involving the HrpX/HrpY two-component system, the HrpS enhancer-binding protein and the HrpL alternate sigma factor. hrpXY is both constitutive and autoregulated; HrpY controls hrpS; and HrpS activates hrpL. These regulatory genes are arranged in the order hrpL, hrpXY and hrpS and constitute three operons. This study describes a novel autoregulatory loop involving HrpS. Genetic experiments using a chromosomal hrpS-lacZ fusion demonstrated that ectopic expression of HrpS increases hrpS transcription and that this effect is blocked by polar mutations in hrpXY and hrpL and by a nonpolar mutation in hrpY. RT-PCR and Northern blot analysis revealed a hrpL-hrpXY polycistronic mRNA. These results suggest that HrpS-mediated autoregulation is due to activation of hrpS by increased levels of HrpY resulting from read-through transcription of hrpXY from the hrpL promoter. This novel autoregulatory loop may serve to rapidly induce hrp genes during infection and to compensate for negative regulatory mechanisms that keep the regulon off in the insect vector. PMID:15751134

  5. The bacterium Pantoea stewartii uses two different type III secretion systems to colonize its plant host and insect vector.

    Science.gov (United States)

    Correa, Valdir R; Majerczak, Doris R; Ammar, El-Desouky; Merighi, Massimo; Pratt, Richard C; Hogenhout, Saskia A; Coplin, David L; Redinbaugh, Margaret G

    2012-09-01

    Plant- and animal-pathogenic bacteria utilize phylogenetically distinct type III secretion systems (T3SS) that produce needle-like injectisomes or pili for the delivery of effector proteins into host cells. Pantoea stewartii subsp. stewartii (herein referred to as P. stewartii), the causative agent of Stewart's bacterial wilt and leaf blight of maize, carries phylogenetically distinct T3SSs. In addition to an Hrc-Hrp T3SS, known to be essential for maize pathogenesis, P. stewartii has a second T3SS (Pantoea secretion island 2 [PSI-2]) that is required for persistence in its flea beetle vector, Chaetocnema pulicaria (Melsh). PSI-2 belongs to the Inv-Mxi-Spa T3SS family, typically found in animal pathogens. Mutagenesis of the PSI-2 psaN gene, which encodes an ATPase essential for secretion of T3SS effectors by the injectisome, greatly reduces both the persistence of P. stewartii in flea beetle guts and the beetle's ability to transmit P. stewartii to maize. Ectopic expression of the psaN gene complements these phenotypes. In addition, the PSI-2 psaN gene is not required for P. stewartii pathogenesis of maize and is transcriptionally upregulated in insects compared to maize tissues. Thus, the Hrp and PSI-2 T3SSs play different roles in the life cycle of P. stewartii as it alternates between its insect vector and plant host. PMID:22773631

  6. A Type III protein-RNA toxin-antitoxin system from Bacillus thuringiensis promotes plasmid retention during spore development.

    Science.gov (United States)

    Short, Francesca L; Monson, Rita E; Salmond, George P C

    2015-01-01

    Members of the Bacillus cereus sensu lato group of bacteria often contain multiple large plasmids, including those encoding virulence factors in B. anthracis. Bacillus species can develop into spores in response to stress. During sporulation the genomic content of the cell is heavily compressed, which could result in counterselection of extrachromosomal genomic elements, unless they have robust stabilization and segregation systems. Toxin-antitoxin (TA) systems are near-ubiquitous in prokaryotes and have multiple biological roles, including plasmid stabilization during vegetative growth. Here, we have shown that a Type III TA system, based on an RNA antitoxin and endoribonuclease toxin, from plasmid pAW63 in Bacillus thuringiensis serovar kurstaki HD-73 can dramatically promote plasmid retention in populations undergoing sporulation and germination, and we provide evidence that this occurs through the post-segregational killing of plasmid-free forespores. Our findings show how an extremely common genetic module can be used to ensure plasmid maintenance during stress-induced developmental transitions, with implications for plasmid dynamics in B. cereus s.l. bacteria.

  7. Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases.

    Science.gov (United States)

    Berryman, Stephen; Moffat, Katy; Harak, Christian; Lohmann, Volker; Jackson, Terry

    2016-08-01

    Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIβ. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIα to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIα and PI4KIIIβ), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes. PMID:27093462

  8. Hijacking of the pleiotropic cytokine interferon-γ by the type III secretion system of Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Claire Gendrin

    Full Text Available Yersinia pestis, the causative agent of bubonic plague, employs its type III secretion system to inject toxins into target cells, a crucial step in infection establishment. LcrV is an essential component of the T3SS of Yersinia spp, and is able to associate at the tip of the secretion needle and take part in the translocation of anti-host effector proteins into the eukaryotic cell cytoplasm. Upon cell contact, LcrV is also released into the surrounding medium where it has been shown to block the normal inflammatory response, although details of this mechanism have remained elusive. In this work, we reveal a key aspect of the immunomodulatory function of LcrV by showing that it interacts directly and with nanomolar affinity with the inflammatory cytokine IFNγ. In addition, we generate specific IFNγ mutants that show decreased interaction capabilities towards LcrV, enabling us to map the interaction region to two basic C-terminal clusters of IFNγ. Lastly, we show that the LcrV-IFNγ interaction can be disrupted by a number of inhibitors, some of which display nanomolar affinity. This study thus not only identifies novel potential inhibitors that could be developed for the control of Yersinia-induced infection, but also highlights the diversity of the strategies used by Y. pestis to evade the immune system, with the hijacking of pleiotropic cytokines being a long-range mechanism that potentially plays a key role in the severity of plague.

  9. Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

    Science.gov (United States)

    Washington, Erica J.; Mukhtar, M. Shahid; Finkel, Omri M.; Wan, Li; Kieber, Joseph J.; Dangl, Jeffery L.

    2016-01-01

    HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis. We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogen-associated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site-specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts. PMID:27274076

  10. Use of amino terminal type III procollagen peptide (P3NP) assay in methotrexate therapy for psoriasis

    Science.gov (United States)

    Khan, S; Subedi, D; Chowdhury, M M U

    2006-01-01

    Hepatic fibrosis continues to be a risk in patients receiving methotrexate for psoriasis. Measurement of amino terminal levels of type III procollagen (P3NP) has been advocated as an effective non‐invasive test for ongoing hepatic fibrogenesis that could avoid liver biopsies. An audit was conducted to assess the practice of P3NP monitoring using guidelines produced by Manchester and whether the agreed levels correlate with histological severity. Sixty five patients with 174 P3NP assays and 30 liver biopsies were reviewed between the years 1999 and 2003. Total number of patient‐methotrexate years was 278.9 and the mean cumulative dose of methotrexate received was 2000 (SD 1838) mg. A higher cumulative dose of methotrexate correlated significantly with high mean and maximum P3NP levels. Of the 30 liver biopsies, 26 (86.6%) showed normal histology or mild to moderate steatosis, three had focal fibrosis, and one had early cirrhosis. A median P3NP value of 5.8 μg/l or higher had a stronger correlation with histological severity. It is concluded that P3NP assay is a valuable adjunct to the clinical management of patients receiving long term methotrexate that can avoid or reduce unnecessary liver biopsies. PMID:16679477

  11. Small-molecule inhibitors suppress the expression of both type III secretion and amylovoran biosynthesis genes in Erwinia amylovora.

    Science.gov (United States)

    Yang, Fan; Korban, Schuyler S; Pusey, P Lawrence; Elofsson, Michael; Sundin, George W; Zhao, Youfu

    2014-01-01

    The type III secretion system (T3SS) and exopolysaccharide (EPS) amylovoran are two essential pathogenicity factors in Erwinia amylovora, the causal agent of the serious bacterial disease fire blight. In this study, small molecules that inhibit T3SS gene expression in E. amylovora under hrp (hypersensitive response and pathogenicity)-inducing conditions were identified and characterized using green fluorescent protein (GFP) as a reporter. These compounds belong to salicylidene acylhydrazides and also inhibit amylovoran production. Microarray analysis of E. amylovora treated with compounds 3 and 9 identified a total of 588 significantly differentially expressed genes. Among them, 95 and 78 genes were activated and suppressed by both compounds, respectively, when compared with the dimethylsulphoxide (DMSO) control. The expression of the majority of T3SS genes in E. amylovora, including hrpL and the avrRpt2 effector gene, was suppressed by both compounds. Compound 3 also suppressed the expression of amylovoran precursor and biosynthesis genes. However, both compounds induced significantly the expression of glycogen biosynthesis genes and siderophore biosynthesis, regulatory and transport genes. Furthermore, many membrane, lipoprotein and exported protein-encoding genes were also activated by both compounds. Similar expression patterns were observed for compounds 1, 2 and 4. Using crab apple flower as a model, compound 3 was capable of reducing disease development in pistils. These results suggest a common inhibition mechanism shared by salicylidene acylhydrazides and indicate that small-molecule inhibitors that disable T3SS function could be explored to control fire blight disease.

  12. Metal binding properties and structure of a type III metallothionein from the metal hyperaccumulator plant Noccaea caerulescens.

    Science.gov (United States)

    Fernandez, Lucia Rubio; Vandenbussche, Guy; Roosens, Nancy; Govaerts, Cédric; Goormaghtigh, Erik; Verbruggen, Nathalie

    2012-09-01

    Metallothioneins (MT) are low molecular weight proteins with cysteine-rich sequences that bind heavy metals with remarkably high affinities. Plant MTs differ from animal ones by a peculiar amino acid sequence organization consisting of two short Cys-rich terminal domains (containing from 4 to 8 Cys each) linked by a Cys free region of about 30 residues. In contrast with the current knowledge on the 3D structure of animal MTs, there is a striking lack of structural data on plant MTs. We have expressed and purified a type III MT from Noccaea caerulescens (previously Thlaspi caerulescens). This protein is able to bind a variety of cations including Cd(2+), Cu(2+), Zn(2+) and Pb(2+), with different stoichiometries as shown by mass spectrometry. The protein displays a complete absence of periodic secondary structures as measured by far-UV circular dichroism, infrared spectroscopy and hydrogen/deuterium exchange kinetics. When attached onto a BIA-ATR biosensor, no significant structural change was observed upon removing the metal ions. PMID:22668884

  13. Abundant type III lipid transfer proteins in Arabidopsis tapetum are secreted to the locule and become a constituent of the pollen exine.

    Science.gov (United States)

    Huang, Ming-Der; Chen, Tung-Ling L; Huang, Anthony H C

    2013-11-01

    Lipid transfer proteins (LTPs) are small secretory proteins in plants with defined lipid-binding structures for possible lipid exocytosis. Special groups of LTPs unique to the anther tapetum are abundant, but their functions are unclear. We studied a special group of LTPs, type III LTPs, in Arabidopsis (Arabidopsis thaliana). Their transcripts were restricted to the anther tapetum, with levels peaking at the developmental stage of maximal pollen-wall exine synthesis. We constructed an LTP-Green Fluorescent Protein (LTP-GFP) plasmid, transformed it into wild-type plants, and monitored LTP-GFP in developing anthers with confocal laser scanning microscopy. LTP-GFP appeared in the tapetum and was secreted via the endoplasmic reticulum-trans-Golgi network machinery into the locule. It then moved to the microspore surface and remained as a component of exine. Immuno-transmission electron microscopy of native LTP in anthers confirmed the LTP-GFP observations. The in vivo association of LTP-GFP and exine in anthers was not observed with non-type III or structurally modified type III LTPs or in transformed exine-defective mutant plants. RNA interference knockdown of individual type III LTPs produced no observable mutant phenotypes. RNA interference knockdown of two type III LTPs produced microscopy-observable morphologic changes in the intine underneath the exine (presumably as a consequence of changes in the exine not observed by transmission electron microscopy) and pollen susceptible to dehydration damage. Overall, we reveal a novel transfer pathway of LTPs in which LTPs bound or nonbound to exine precursors are secreted from the tapetum to become microspore exine constituents; this pathway explains the need for plentiful LTPs to incorporate into the abundant exine. PMID:24096413

  14. Profile of differentially expressed genes mediated by the type III epidermal growth factor receptor mutation expressed in a small-cell lung cancer cell line

    DEFF Research Database (Denmark)

    Pedersen, M.W.; Andersen, Thomas Thykjær; Ørntoft, Torben Falck;

    2001-01-01

    Previous studies have shown a correlation between expression of the EGF receptor type III mutation (EGFRvIII) and a more malignant phenotype of various cancers including: non-small-cell lung cancer, glioblastoma multiforme, prostate cancer and breast cancer. Thus, a detailed molecular genetic...... understanding of how the EGFRvIII contributes to the malignant phenotype is of major importance for future therapy. The GeneChip Hu6800Set developed by Affymetrix was used to identify changes in gene expression caused by the expression of EGFRvIII. The cell line selected for the study was an EGF receptor...... negative small-cell-lung cancer cell line, GLC3, stably transfected with the EGFRvIII gene in a Tet-On system. By comparison of mRNA levels in EGFRvIII-GLC3 with those of Tet-On-GLC3, it was found that the levels of mRNAs encoding several transcription factors (ATF-3, JunD, and c-Myb), cell adhesion...

  15. Development, validation, and utilization of a novel antibody specific to the type III chicken gonadotropin-releasing hormone receptor.

    Science.gov (United States)

    McFarlane, H O; Joseph, N T; Maddineni, S R; Ramachandran, R; Bédécarrats, G Y

    2011-02-01

    Two gonadotropin-releasing hormone receptors (GnRH-Rs) have been characterized in chickens to date: cGnRH-R-I and cGnRH-R-III, with cGnRH-R-III being the predominant pituitary form. The purpose of the present study was to first validate a novel antibody for the specific detection of cGnRH-R-III and second, using this antibody, detect changes in cGnRH-R-III protein levels in the pituitary gland of male and female chickens during a reproductive cycle. The localization of cGnRH-R-III within the anterior pituitary gland was also determined. Western blotting of pituitary extracts and transiently transfected COS-7 cell lysates revealed that our antibody is highly specific to cGnRH-R-III protein. Similarly, when used in immunocytochemistry, this antibody specifically detects cells expressing cGnRH-R-III and not cGnRH-R-I. Western blot analyses of chicken pituitary gland homogenates show that cGnRH-R-III protein levels are significantly greater in sexually mature birds than in immature birds or birds at the end of a reproductive cycle (P chickens. PMID:21093197

  16. Key steps in type III secretion system (T3SS) towards translocon assembly with potential sensor at plant plasma membrane.

    Science.gov (United States)

    Ji, Hongtao; Dong, Hansong

    2015-09-01

    Many plant- and animal-pathogenic Gram-negative bacteria employ the type III secretion system (T3SS) to translocate effector proteins from bacterial cells into the cytosol of eukaryotic host cells. The effector translocation occurs through an integral component of T3SS, the channel-like translocon, assembled by hydrophilic and hydrophobic proteinaceous translocators in a two-step process. In the first, hydrophilic translocators localize to the tip of a proteinaceous needle in animal pathogens, or a proteinaceous pilus in plant pathogens, and associate with hydrophobic translocators, which insert into host plasma membranes in the second step. However, the pilus needs to penetrate plant cell walls in advance. All hydrophilic translocators so far identified in plant pathogens are characteristic of harpins: T3SS accessory proteins containing a unitary hydrophilic domain or an additional enzymatic domain. Two-domain harpins carrying a pectate lyase domain potentially target plant cell walls and facilitate the penetration of the pectin-rich middle lamella by the bacterial pilus. One-domain harpins target plant plasma membranes and may play a crucial role in translocon assembly, which may also involve contrapuntal associations of hydrophobic translocators. In all cases, sensory components in the target plasma membrane are indispensable for the membrane recognition of translocators and the functionality of the translocon. The conjectural sensors point to membrane lipids and proteins, and a phosphatidic acid and an aquaporin are able to interact with selected harpin-type translocators. Interactions between translocators and their sensors at the target plasma membrane are assumed to be critical for translocon assembly.

  17. Acquired type III secretion system determines environmental fitness of epidemic Vibrio parahaemolyticus in the interaction with bacterivorous protists.

    Directory of Open Access Journals (Sweden)

    Carsten Matz

    Full Text Available Genome analyses of marine microbial communities have revealed the widespread occurrence of genomic islands (GIs, many of which encode for protein secretion machineries described in the context of bacteria-eukaryote interactions. Yet experimental support for the specific roles of such GIs in aquatic community interactions remains scarce. Here, we test for the contribution of type III secretion systems (T3SS to the environmental fitness of epidemic Vibrio parahaemolyticus. Comparisons of V. parahaemolyticus wild types and T3SS-defective mutants demonstrate that the T3SS encoded on genome island VPaI-7 (T3SS-2 promotes survival of V. parahaemolyticus in the interaction with diverse protist taxa. Enhanced persistence was found to be due to T3SS-2 mediated cytotoxicity and facultative parasitism of V. parahaemolyticus on coexisting protists. Growth in the presence of bacterivorous protists and the T3SS-2 genotype showed a strong correlation across environmental and clinical isolates of V. parahaemolyticus. Short-term microcosm experiments provide evidence that protistan hosts facilitate the invasion of T3SS-2 positive V. parahaemolyticus into a coastal plankton community, and that water temperature and productivity further promote enhanced survival of T3SS-2 positive V. parahaemolyticus. This study is the first to describe the fitness advantage of GI-encoded functions in a microbial food web, which may provide a mechanistic explanation for the global spread and the seasonal dynamics of V. parahaemolyticus pathotypes, including the pandemic serotype cluster O3:K6, in aquatic environments.

  18. The 33 carboxyl-terminal residues of Spa40 orchestrate the multi-step assembly process of the type III secretion needle complex in Shigella flexneri

    NARCIS (Netherlands)

    Botteaux, Anne; Kayath, Christian A.; Page, Anne-Laure; Jouihri, Nouredine; Sani, Musa; Boekema, Egbert; Biskri, Latefa; Parsot, Claude; Allaoui, Abdelmounaaim

    2010-01-01

    The type III secretion apparatus (T3SA) is a central virulence factor of many Gram-negative bacteria. Its overall morphology consists of a cytoplasmic region, inner- and outer-membrane sections and an extracellular needle. In Shigella, the length of the needle is regulated by Spa32. To understand be

  19. Closing the circle on the discovery of genes encoding Hrp regulon members and type III secretion system effectors in the genomes of three model Pseudomonas syringae strains

    Science.gov (United States)

    Pseudomonas syringae strains translocate large and distinct collections of effector proteins into plant cells via the type III secretion system (T3SS). P. syringae effectors are designated Hop (Hrp outer protein) or Avr (avirulence) proteins. Some Hop proteins are considered to be extracellular T3...

  20. Joint inflammation and chondrocyte death become independent of Fcgamma receptor type III by local overexpression of interferon-gamma during immune complex-mediated arthritis.

    NARCIS (Netherlands)

    Nabbe, K.C.A.M.; Boross, P.; Holthuysen, A.E.M.; Sloetjes, A.W.; Kolls, J.; Verbeek, S.; Lent, P.L.E.M. van; Berg, W.B. van den

    2005-01-01

    OBJECTIVE: It has previously been shown that the onset and the degree of joint inflammation during immune complex (IC)-mediated arthritis depend on Fcgamma receptor type III (FcgammaRIII). Local adenoviral overexpression of interferon-gamma (IFNgamma) in the knee joint prior to onset of IC-mediated

  1. Search for type-III Seesaw heavy leptons in $pp$ collisions at $\\sqrt{s}= 8$ TeV with the ATLAS Detector

    CERN Document Server

    Aad, Georges; Abdallah, Jalal; Abdinov, Ovsat; Aben, Rosemarie; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Affolder, Tony; Agatonovic-Jovin, Tatjana; Aguilar-Saavedra, Juan Antonio; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Alkire, Steven Patrick; Allbrooke, Benedict; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Άlvarez Piqueras, Damián; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; 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Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertolucci, Federico; Bertsche, Carolyn; Bertsche, David; Besana, Maria Ilaria; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Betancourt, Christopher; Bethke, Siegfried; Bevan, Adrian John; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Biglietti, Michela; Bilbao De Mendizabal, Javier; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Black, Curtis; Black, James; Black, Kevin; Blackburn, Daniel; Blair, Robert; Blanchard, Jean-Baptiste; Blanco, Jacobo Ezequiel; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boehler, Michael; Bogaerts, Joannes Andreas; Bogavac, Danijela; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Boldyrev, Alexey; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozic, Ivan; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Breaden Madden, William Dmitri; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Bristow, Kieran; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Brown, Jonathan; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Bruscino, Nello; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Buehrer, Felix; Bugge, Lars; Bugge, Magnar Kopangen; Bulekov, Oleg; Bullock, Daniel; Burckhart, Helfried; Burdin, Sergey; Burghgrave, Blake; Burke, Stephen; Burmeister, Ingo; Busato, Emmanuel; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Butler, John; Butt, Aatif Imtiaz; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; Cabrera Urbán, Susana; Caforio, Davide; Cairo, Valentina; Cakir, Orhan; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Caloba, Luiz; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarda, Stefano; Camarri, Paolo; Cameron, David; Caminada, Lea Michaela; Caminal Armadans, Roger; Campana, Simone; Campanelli, Mario; Campoverde, Angel; Canale, Vincenzo; Canepa, Anadi; Cano Bret, Marc; Cantero, Josu; Cantrill, Robert; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Cardillo, Fabio; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Castaneda-Miranda, Elizabeth; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerio, Benjamin; Cerny, Karel; Cerqueira, Augusto Santiago; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chang, Philip; Chapleau, Bertrand; Chapman, John Derek; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Liming; Chen, Shenjian; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Yangyang; Cheplakov, Alexander; Cheremushkina, Evgenia; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Childers, John Taylor; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Choi, Kyungeon; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christodoulou, Valentinos; Chromek-Burckhart, Doris; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioara, Irina Antonela; Ciocio, Alessandra; Citron, Zvi Hirsh; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Philip James; Clarke, Robert; Cleland, Bill; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Cogan, Joshua Godfrey; Cole, Brian; Cole, Stephen; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey Rogers; Dang, Nguyen Phuong; Daniells, Andrew Christopher; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Deigaard, Ingrid; Del Peso, Jose; Del Prete, Tarcisio; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; do Vale, Maria Aline Barros; Dobos, Daniel; Dobre, Monica; Doglioni, Caterina; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dyndal, Mateusz; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Erdmann, Johannes; Ereditato, Antonio; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Feremenga, Last; Fernandez Martinez, Patricia; Fernandez Perez, Sonia; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Fitzgerald, Eric Andrew; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Fletcher, Rob Roy MacGregor; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Francis, David; Franconi, Laura; Franklin, Melissa; Frate, Meghan; Fraternali, Marco; Freeborn, David; French, Sky; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gao, Jun; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Geisler, Manuel Patrice; Gemme, Claudia; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghazlane, Hamid; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gibbard, Bruce; Gibson, Stephen; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giromini, Paolo; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Gozani, Eitan; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Guan, Liang; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Gupta, Shaun; Gustavino, Giuliano; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageböck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Hall, David; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Hanke, Paul; Hanna, Remie; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrington, Robert; Harrison, Paul Fraser; Hartjes, Fred; Hasegawa, Makoto; Hasegawa, Satoshi; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Hejbal, Jiri; Helary, Louis; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Heng, Yang; Hengler, Christopher; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hinman, Rachel Reisner; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohlfeld, Marc; Hohn, David; Holmes, Tova Ray; Homann, Michael; Hong, Tae Min; Hooft van Huysduynen, Loek; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Catherine; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Qipeng; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Ilchenko, Iurii; Iliadis, Dimitrios; Ilic, Nikolina; Inamaru, Yuki; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Ivarsson, Jenny; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansky, Roland; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanty, Laura; Jejelava, Juansher; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Yi; Jiggins, Stephen; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Per; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Jung, Christian; Jussel, Patrick; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kahn, Sebastien Jonathan; Kajomovitz, Enrique; Kalderon, Charles William; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karamaoun, Andrew; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karnevskiy, Mikhail; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katre, Akshay; Katzy, Judith; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keller, John; Kempster, Jacob Julian; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharlamov, Alexey; Khoo, Teng Jian; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hee Yeun; Kim, Hyeon Jin; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; King, Matthew; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kiuchi, Kenji; Kivernyk, Oleh; Kladiva, Eduard; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; König, Sebastian; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kurumida, Rie; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, J örn Christian; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Lazovich, Tomo; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeBlanc, Matthew Edgar; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leisos, Antonios; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Haifeng; Li, Ho Ling; Li, Lei; Li, Liang; Li, Shu; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Liblong, Aaron; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Hao; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan David; Long, Robin Eamonn; Looper, Kristina Anne; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lopez Paz, Ivan; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lösel, Philipp Jonathan; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Nan; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maier, Thomas; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mantoani, Matteo; Mapelli, Livio; March, Luis; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marjanovic, Marija; Marley, Daniel; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massa, Lorenzo; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazza, Simone Michele; Mazzaferro, Luca; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McPherson, Robert; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Middleton, Robin; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Mohapatra, Soumya; Mohr, Wolfgang; Molander, Simon; Moles-Valls, Regina; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Mortensen, Simon Stark; Morton, Alexander; Morvaj, Ljiljana; Mosidze, Maia; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Ralph Soeren Peter; Mueller, Thibaut; Muenstermann, Daniel; Mullen, Paul; Mullier, Geoffrey; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Nef, Pascal Daniel; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsen, Jon Kerr; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nomachi, Masaharu; Nomidis, Ioannis; Nooney, Tamsin; Norberg, Scarlet; Nordberg, Markus; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'Brien, Brendan Joseph; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paganis, Efstathios; Pahl, Christoph; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Palma, Alberto; Pan, Yibin; Panagiotopoulou, Evgenia; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Pauly, Thilo; Pearce, James; Pearson, Benjamin; Pedersen, Lars Egholm; Pedersen, Maiken; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penwell, John; Perepelitsa, Dennis; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Pettersson, Nora Emilia; Pezoa, Raquel; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Pickering, Mark Andrew; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinfold, James; Pingel, Almut; Pinto, Belmiro; Pires, Sylvestre; Pitt, Michael; Pizio, Caterina; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Plucinski, Pawel; Pluth, Daniel; Poettgen, Ruth; Poggioli, Luc; Pohl, David-leon; Polesello, Giacomo; Poley, Anne-luise; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Prell, Soeren; Price, Darren; Price, Lawrence; Primavera, Margherita; Prince, Sebastien; Proissl, Manuel; Prokofiev, Kirill; Prokoshin, Fedor; Protopapadaki, Eftychia-sofia; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Ptacek, Elizabeth; Puddu, Daniele; Pueschel, Elisa; Puldon, David; Purohit, Milind; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Quarrie, David; Quayle, William; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Raddum, Silje; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Rajagopalan, Srinivasan; Rammensee, Michael; Rangel-Smith, Camila; Rauscher, Felix; Rave, Stefan; Ravenscroft, Thomas; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Rehnisch, Laura; Reisin, Hernan; Relich, Matthew; Rembser, Christoph; Ren, Huan; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Roda, Chiara; Roe, Shaun; Røhne, Ole; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Rachel; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Rud, Viacheslav; Rudolph, Christian; Rudolph, Matthew Scott; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Ruschke, Alexander; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Saddique, Asif; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saimpert, Matthias; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Sanchez, Arturo; Sánchez, Javier; Sanchez Martinez, Victoria; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sannino, Mario; Sansoni, Andrea; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; 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Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schwegler, Philipp; Schweiger, Hansdieter; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Sciacca, Gianfranco; Scifo, Estelle; Sciolla, Gabriella; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Seliverstov, Dmitry; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Serre, Thomas; Sessa, Marco; Seuster, Rolf; Severini, Horst; Sfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyedruhollah; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Shushkevich, Stanislav; Sicho, Petr; Sidiropoulou, Ourania; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silver, Yiftah; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Dorian; Simoniello, Rosa; Sinervo, Pekka; Sinev, Nikolai; Siragusa, Giovanni; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinner, Malcolm Bruce; Skottowe, Hugh Philip; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Matthew; Smith, Russell; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snidero, Giacomo; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Song, Hong Ye; Soni, Nitesh; Sood, Alexander; Sopczak, Andre; Sopko, Bruno; Sopko, Vit; Sorin, Veronica; Sosa, David; Sosebee, Mark; Sotiropoulou, Calliope Louisa; Soualah, Rachik; Soukharev, Andrey; South, David; Sowden, Benjamin; Spagnolo, Stefania; Spalla, Margherita; Spanò, Francesco; Spearman, William Robert; Spettel, Fabian; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; Spreitzer, Teresa; St Denis, Richard Dante; Staerz, Steffen; Stahlman, Jonathan; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Stavina, Pavel; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramaniam, Rajivalochan; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Shota; Suzuki, Yu; Svatos, Michal; Swedish, Stephen; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Taccini, Cecilia; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tam, Jason; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Shuji; Tannenwald, Benjamin Bordy; Tannoury, Nancy; Tapprogge, Stefan; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Ray; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thun, Rudolf; Tibbetts, Mark James; Ticse Torres, Royer Edson; 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Zoccoli, Antonio; zur Nedden, Martin; Zurzolo, Giovanni; Zwalinski, Lukasz

    2015-01-01

    A search for the pair-production of heavy leptons ($N^0,L^{\\pm}$) predicted by the type-III seesaw theory formulated to explain the origin of small neutrino masses is presented. The decay channels $N^0\\rightarrow W^{\\pm}l^{\\mp}$ ($\\ell = e, \\mu, \\tau$) and $L^{\\pm}\\rightarrow W^\\pm \

  2. Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C

    DEFF Research Database (Denmark)

    Nielsen, Mette J.; Veidal, Sanne S.; Karsdal, Morten A.;

    2015-01-01

    BACKGROUND & AIMS: Fibrogenesis results in release of certain extracellular matrix protein fragments into the circulation. We evaluated the diagnostic and prognostic performance of two novel serological markers, the precisely cleaved N-terminal propeptide of type III collagen (Pro-C3) and a peptide...

  3. Towards an entirely endovascular aortic world: an update of techniques and outcomes for endovascular and open treatment of type I, II, and III endoleaks.

    Science.gov (United States)

    Mangialardi, Nicola; Orrico, Matteo; Ronchey, Sonia; Praquin, Barbara; Alberti, Vittorio; Setacci, Carlo

    2016-10-01

    Endovascular aneurysm repair (EVAR) is largely the most adopted strategy for aneurysmal disease of the aorta. Nevertheless, the high incidence of reintervention makes it difficult to identify EVAR as a definitive solution; in particular, the most frequent indication of reintervention is endoleak, which is defined as persistent flow into the aneurysmal sac from different sources. Several treatment strategies are described. A contemporary literature search was performed with the intent of describing techniques and outcomes of endovascular and open strategies to type I, II, and III endoleak. Described techniques and outcomes were organized by indication (type I, II, and III endoleak) and by type of approach (endovascular, open, and laparoscopic) to give an overview of the current status of the treatment for the three most frequent types of endoleak. Several endovascular means are described in the literature for the treatment of endoleak. PMID:27465391

  4. Lysosomal storage of heparan sulfate causes mitochondrial defects, altered autophagy, and neuronal death in the mouse model of mucopolysaccharidosis III type C.

    Science.gov (United States)

    Pshezhetsky, Alexey V

    2016-06-01

    The genetic metabolic disease mucopolysaccharidosis III type C (MPS IIIC, Sanfilippo disease type C) causes progressive neurodegeneration in infants and children, leading to dementia and death before adulthood. MPS IIIC stands out among lysosomal diseases because it is the only one caused by a deficiency not of a hydrolase but of HGSNAT (heparan--glucosaminide N-acetyltransferase), which catalyzes acetylation of glycosaminoglycan heparan sulfate (HS) prior to its hydrolysis. PMID:25998837

  5. New method of identification of I and III collagen types at forming fibril framework of mesonephros and metanephros of human embryos

    OpenAIRE

    Boyko T.A.; Shapovalova Ye.Yu.

    2009-01-01

    Becoming of collagen composition of fibril framework of meso- and metanephros was studied by the method of immunohistochemistry and lectinochistochemistry on 124 human embryos in age from 21 days to 12 weeks of intrauterine development. Embryos were fixed in formalin and embedded in the paraffin. Primary antibodies were monoclonal antibodies to the collagen type I and III. Lectins of Perca fluviatilis and Vica Alba were used. It is received, that collagen fibers type I were stained by lectin ...

  6. Impairment of type I but not type III IFN signaling by hepatitis C virus infection influences antiviral responses in primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Jacques Friborg

    Full Text Available Peginterferon lambda-1a (Lambda, a type III interferon (IFN, acts through a unique receptor complex with limited cellular expression outside the liver which may result in a differentiated tolerability profile compared to peginterferon alfa (alfa. In Phase 2b clinical studies, Lambda administered in combination with ribavirin (RBV was efficacious in patients with hepatitis C virus (HCV infection representing genotypes 1 through 4, and was associated with more rapid declines in HCV RNA compared to alfa plus RBV. To gain insights into potential mechanisms for this finding, we investigated the effects of HCV replication on IFN signaling in primary human hepatocytes (PHH and in induced hepatocyte-like cells (iHLCs. HCV infection resulted in rapid down-regulation of the type I IFN-α receptor subunit 1 (IFNAR1 transcript in hepatocytes while the transcriptional level of the unique IFN-λ receptor subunit IL28RA was transiently increased. In line with this observation, IFN signaling was selectively impaired in infected cells upon stimulation with alfa but not in response to Lambda. Importantly, in contrast to alfa, Lambda was able to induce IFN-stimulated gene (ISG expression in HCV-infected hepatocytes, reflecting the onset of innate responses. Moreover, global transcriptome analysis in hepatocytes indicated that Lambda stimulation prolonged the expression of various ISGs that are potentially beneficial to antiviral defense mechanisms. Collectively, these observed effects of HCV infection on IFN receptor expression and signaling within infected hepatocytes provide a possible explanation for the more pronounced early virologic responses observed in patients treated with Lambda compared to alfa.

  7. Fraturas supracondilares tipo III do úmero em crianças: tratamento com braço reto Type III supracondylar fractures of the humerus in children: straight-arm treatment

    Directory of Open Access Journals (Sweden)

    Jamish Gandhi

    2010-01-01

    Full Text Available INTRODUÇÃO: As fraturas supracondilares de Gartland tipo III são as lesões comuns em crianças. Apresentamos um método de redução manipulativa, imobilização e fixação usando gesso-de-Paris, com o cotovelo em extensão total (braço reto. MÉTODO: Estudo retrospectivo analisando todos os pacientes com fraturas supracondilares de Gartland tipo III no Wellington Public Hospital, durante o período de fevereiro de 1999 a março de 2007. Os sete pacientes foram tratados pela técnica do braço reto, e os desfechos clínicos foram revisados neste estudo. RESULTADO: Todos os pais ficaram satisfeitos com os resultados. Usando os critérios de Flynn,6 seis pacientes atingiram excelentes resultados e um teve resultado bom quando se analisou o ângulo de alinhamento. Ao verificar a amplitude de movimento, quatro pacientes tiveram resultados bons, um moderado e dois, ruim. CONCLUSÃO: O tratamento com braço reto das fraturas supracondilares de Gartland tipo III parece ser uma alternativa não-invasiva e segura da fixação com fio K.OBJECTIVE: Gartland type III supracondylar fractures are a common injury in children. We present a method of manipulative reduction, immobilization and fixation using Plaster of Paris with the elbow in full extension (straight-arm. METHOD: Retrospective study analyzing all patients with Gartland type III supracondylar fractures at the Wellington Public Hospital during the period from February 1999 to March 2007. The seven patients had been treated with the straight-arm technique, and the clinical outcomes are reviewed in this study. RESULT: All the parents were satisfied with the results. Using the Flynn criteria6, six patients achieved excellent results and one good, in relation to the carrying angle. With regard to the range of motion, four patients had good results, one fair, and two poor. CONCLUSION: Straight-arm treatment of Gartland type III supracondylar fractures appears to be a non-invasive and safe

  8. Off-diagonal terms in Yukawa textures of the Type-III 2-Higgs doublet model and light charged Higgs boson phenomenology

    CERN Document Server

    Hernández-Sánchez, J; Noriega-Papaqui, R; Rosado, A

    2013-01-01

    We discuss flavor-violating constraints and consequently possible charged Higgs boson phenomenology emerging from a four-zero Yukawa texture embedded within the Type-III 2-Higgs Doublet Model (2HDM-III). Firstly, we show in detail how we can obtain several kinds of 2HDMs when some parameters in the Yukawa texture are absent. Secondly, we present a comprehensive study of the main $B$-physics constraints on such parameters induced by flavor-changing processes, in particular on the off-diagonal terms of such a texture: i.e., from $\\mu -e$ universality in $\\tau$ decays, several leptonic B-decays ($B \\to \\tau \

  9. Perturbation of maize phenylpropanoid metabolism by an AvrE family type III effector from Pantoea stewartii.

    Science.gov (United States)

    Asselin, Jo Ann E; Lin, Jinshan; Perez-Quintero, Alvaro L; Gentzel, Irene; Majerczak, Doris; Opiyo, Stephen O; Zhao, Wanying; Paek, Seung-Mann; Kim, Min Gab; Coplin, David L; Blakeslee, Joshua J; Mackey, David

    2015-03-01

    AvrE family type III effector proteins share the ability to suppress host defenses, induce disease-associated cell death, and promote bacterial growth. However, despite widespread contributions to numerous bacterial diseases in agriculturally important plants, the mode of action of these effectors remains largely unknown. WtsE is an AvrE family member required for the ability of Pantoea stewartii ssp. stewartii (Pnss) to proliferate efficiently and cause wilt and leaf blight symptoms in maize (Zea mays) plants. Notably, when WtsE is delivered by a heterologous system into the leaf cells of susceptible maize seedlings, it alone produces water-soaked disease symptoms reminiscent of those produced by Pnss. Thus, WtsE is a pathogenicity and virulence factor in maize, and an Escherichia coli heterologous delivery system can be used to study the activity of WtsE in isolation from other factors produced by Pnss. Transcriptional profiling of maize revealed the effects of WtsE, including induction of genes involved in secondary metabolism and suppression of genes involved in photosynthesis. Targeted metabolite quantification revealed that WtsE perturbs maize metabolism, including the induction of coumaroyl tyramine. The ability of mutant WtsE derivatives to elicit transcriptional and metabolic changes in susceptible maize seedlings correlated with their ability to promote disease. Furthermore, chemical inhibitors that block metabolic flux into the phenylpropanoid pathways targeted by WtsE also disrupted the pathogenicity and virulence activity of WtsE. While numerous metabolites produced downstream of the shikimate pathway are known to promote plant defense, our results indicate that misregulated induction of phenylpropanoid metabolism also can be used to promote pathogen virulence. PMID:25635112

  10. Perturbation of Maize Phenylpropanoid Metabolism by an AvrE Family Type III Effector from Pantoea stewartii1[OPEN

    Science.gov (United States)

    Asselin, Jo Ann E.; Lin, Jinshan; Perez-Quintero, Alvaro L.; Gentzel, Irene; Majerczak, Doris; Opiyo, Stephen O.; Zhao, Wanying; Paek, Seung-Mann; Kim, Min Gab; Coplin, David L.; Blakeslee, Joshua J.; Mackey, David

    2015-01-01

    AvrE family type III effector proteins share the ability to suppress host defenses, induce disease-associated cell death, and promote bacterial growth. However, despite widespread contributions to numerous bacterial diseases in agriculturally important plants, the mode of action of these effectors remains largely unknown. WtsE is an AvrE family member required for the ability of Pantoea stewartii ssp. stewartii (Pnss) to proliferate efficiently and cause wilt and leaf blight symptoms in maize (Zea mays) plants. Notably, when WtsE is delivered by a heterologous system into the leaf cells of susceptible maize seedlings, it alone produces water-soaked disease symptoms reminiscent of those produced by Pnss. Thus, WtsE is a pathogenicity and virulence factor in maize, and an Escherichia coli heterologous delivery system can be used to study the activity of WtsE in isolation from other factors produced by Pnss. Transcriptional profiling of maize revealed the effects of WtsE, including induction of genes involved in secondary metabolism and suppression of genes involved in photosynthesis. Targeted metabolite quantification revealed that WtsE perturbs maize metabolism, including the induction of coumaroyl tyramine. The ability of mutant WtsE derivatives to elicit transcriptional and metabolic changes in susceptible maize seedlings correlated with their ability to promote disease. Furthermore, chemical inhibitors that block metabolic flux into the phenylpropanoid pathways targeted by WtsE also disrupted the pathogenicity and virulence activity of WtsE. While numerous metabolites produced downstream of the shikimate pathway are known to promote plant defense, our results indicate that misregulated induction of phenylpropanoid metabolism also can be used to promote pathogen virulence. PMID:25635112

  11. Supramolecular structure and functional analysis of the type III secretion system in Pseudomonas fluorescens 2P24

    Directory of Open Access Journals (Sweden)

    Ping eLiu

    2016-01-01

    Full Text Available The type III secretion system (T3SS of plant and animal bacterial pathogens directs the secretion and injection of proteins into host cells. Some homologous genes of T3SS were found also in nonpathogenic bacteria, but the organization of its machinery and basic function are still unknown. In this study, we identified a T3SS gene cluster from the plant growth-promoting Pseudomonas fluorescens 2P24 and isolated the corresponding T3SS apparatus. The T3SS gene cluster of strain 2P24 is similar organizationally to that of pathogenic P. syringae, except that it lacks the regulator hrpR and the hrpK1 and hrpH genes, which are involved in translocation of proteins. Electron microscopy revealed that the T3SS supramolecular structure of strain 2P24 was comprised of two distinctive substructures: a long extracellular, filamentous pilus and a membrane-embedded base. We show that strain 2P24 deploys a harpin homologue protein, RspZ1, to elicit a hypersensitive response when infiltrated into Nicotiana tabacum cv. xanthi leaves with protein that is partially purified, and by complementing the hrpZ1 mutation of pHIR11. The T3SS of strain 2P24 retained ability to secrete effectors, whereas its effector translocation activity appeared to be excessively lost. Mutation of the rscC gene from 2P24 T3SS abolished the secretion of effectors, but the general biocontrol properties were unaffected. Remarkably, strain 2P24 induced functional MAMP-triggered immunity that included a burst of reactive oxygen species, strong suppression of challenge cell death, and disease expansion, while it was not associated with the secretion functional T3SS.

  12. Supramolecular Structure and Functional Analysis of the Type III Secretion System in Pseudomonas fluorescens 2P24.

    Science.gov (United States)

    Liu, Ping; Zhang, Wei; Zhang, Li-Qun; Liu, Xingzhong; Wei, Hai-Lei

    2015-01-01

    The type III secretion system (T3SS) of plant and animal bacterial pathogens directs the secretion and injection of proteins into host cells. Some homologous genes of T3SS were found also in non-pathogenic bacteria, but the organization of its machinery and basic function are still unknown. In this study, we identified a T3SS gene cluster from the plant growth-promoting Pseudomonas fluorescens 2P24 and isolated the corresponding T3SS apparatus. The T3SS gene cluster of strain 2P24 is similar organizationally to that of pathogenic P. syringae, except that it lacks the regulator hrpR and the hrpK1 and hrpH genes, which are involved in translocation of proteins. Electron microscopy revealed that the T3SS supramolecular structure of strain 2P24 was comprised of two distinctive substructures: a long extracellular, filamentous pilus, and a membrane-embedded base. We show that strain 2P24 deploys a harpin homolog protein, RspZ1, to elicit a hypersensitive response when infiltrated into Nicotiana tabacum cv. xanthi leaves with protein that is partially purified, and by complementing the hrpZ1 mutation of pHIR11. The T3SS of strain 2P24 retained ability to secrete effectors, whereas its effector translocation activity appeared to be excessively lost. Mutation of the rscC gene from 2P24 T3SS abolished the secretion of effectors, but the general biocontrol properties were unaffected. Remarkably, strain 2P24 induced functional MAMP-triggered immunity that included a burst of reactive oxygen species, strong suppression of challenge cell death, and disease expansion, while it was not associated with the secretion functional T3SS. PMID:26779224

  13. Genetic inviability is a major driver of type III survivorship in experimental families of a highly fecund marine bivalve.

    Science.gov (United States)

    Plough, L V; Shin, G; Hedgecock, D

    2016-02-01

    The offspring of most highly fecund marine fish and shellfish suffer substantial mortality early in the life cycle, complicating prediction of recruitment and fisheries management. Early mortality has long been attributed to environmental factors and almost never to genetic sources. Previous work on a variety of marine bivalve species uncovered substantial genetic inviability among the offspring of inbred crosses, suggesting a large load of early-acting deleterious recessive mutations. However, genetic inviability of randomly bred offspring has not been addressed. Here, genome-wide surveys reveal widespread, genotype-dependent mortality in randomly bred, full-sib progenies of wild-caught Pacific oysters (Crassostrea gigas). Using gene-mapping methods, we infer that 11-19 detrimental alleles per family render 97.9-99.8% of progeny inviable. The variable genomic positions of viability loci among families imply a surprisingly large load of partially dominant or additive detrimental mutations in wild adult oysters. Although caution is required in interpreting the relevance of experimental results for natural field environments, we argue that the observed genetic inviability corresponds with type III survivorship, which is characteristic of both hatchery and field environments and that our results, therefore, suggest the need for additional experiments under the near-natural conditions of mesocosms. We explore the population genetic implications of our results, calculating a detrimental mutation rate that is comparable to that estimated for conifers and other highly fecund perennial plants. Genetic inviability ought to be considered as a potential major source of low and variable recruitment in highly fecund marine animals.

  14. Characterization of the N-terminal domain of BteA: a Bordetella type III secreted cytotoxic effector.

    Directory of Open Access Journals (Sweden)

    Chen Guttman

    Full Text Available BteA, a 69-kDa cytotoxic protein, is a type III secretion system (T3SS effector in the classical Bordetella, the etiological agents of pertussis and related mammalian respiratory diseases. Currently there is limited information regarding the structure of BteA or its subdomains, and no insight as to the identity of its eukaryotic partners(s and their modes of interaction with BteA. The mechanisms that lead to BteA dependent cell death also remain elusive. The N-terminal domain of BteA is multifunctional, acting as a docking platform for its cognate chaperone (BtcA in the bacterium, and targeting the protein to lipid raft microdomains within the eukaryotic host cell. In this study we describe the biochemical and biophysical characteristics of this domain (BteA287 and determine its architecture. We characterize BteA287 as being a soluble and highly stable domain which is rich in alpha helical content. Nuclear magnetic resonance (NMR experiments combined with size exclusion and analytical ultracentrifugation measurements confirm these observations and reveal BteA287 to be monomeric in nature with a tendency to oligomerize at concentrations above 200 µM. Furthermore, diffusion-NMR demonstrated that the first 31 residues of BteA287 are responsible for the apparent aggregation behavior of BteA287. Light scattering analyses and small angle X-ray scattering experiments reveal a prolate ellipsoidal bi-pyramidal dumb-bell shape. Thus, our biophysical characterization is a first step towards structure determination of the BteA N-terminal domain.

  15. Efficient isolation of Pseudomonas aeruginosa type III secretion translocators and assembly of heteromeric transmembrane pores in model membranes.

    Science.gov (United States)

    Romano, Fabian B; Rossi, Kyle C; Savva, Christos G; Holzenburg, Andreas; Clerico, Eugenia M; Heuck, Alejandro P

    2011-08-23

    Translocation of bacterial toxins or effectors into host cells using the type III secretion (T3S) system is a conserved mechanism shared by many Gram-negative pathogens. Pseudomonas aeruginosa injects different proteins across the plasma membrane of target cells, altering the normal metabolism of the host. Protein translocation presumably occurs through a proteinaceous transmembrane pore formed by two T3S secreted protein translocators, PopB and PopD. Unfolded translocators are secreted through the T3S needle prior to insertion into the target membrane. Purified PopB and PopD form pores in model membranes. However, their tendency to form heterogeneous aggregates in solution had hampered the analysis of how these proteins undergo the transition from a denatured state to a membrane-inserted state. Translocators were purified as stable complexes with the cognate chaperone PcrH and isolated from the chaperone using 6 M urea. We report here the assembly of stable transmembrane pores by dilution of urea-denatured translocators in the presence of membranes. PopB and PopD spontaneously bound liposomes containing anionic phospholipids and cholesterol in a pH-dependent manner as observed by two independent assays, time-resolved Förster resonance energy transfer and sucrose-step gradient ultracentrifugation. Using Bodipy-labeled proteins, we found that PopB interacts with PopD on the membrane surface as determined by excitation energy migration and fluorescence quenching. Stable transmembrane pores are more efficiently assembled at pH <5.0, suggesting that acidic residues might be involved in the initial membrane binding and/or insertion. Altogether, the experimental setup described here represents an efficient method for the reconstitution and analysis of membrane-inserted translocators.

  16. Fitness Cost of Fluoroquinolone Resistance in Clinical Isolates of Pseudomonas aeruginosa Differs by Type III Secretion Genotype

    Science.gov (United States)

    Agnello, Melissa; Finkel, Steven E.; Wong-Beringer, Annie

    2016-01-01

    Fluoroquinolone (FQ) resistance is highly prevalent among clinical strains of Pseudomonas aeruginosa, limiting treatment options. We have reported previously that highly virulent strains containing the exoU gene of the type III secretion system are more likely to be FQ-resistant than strains containing the exoS gene, as well as more likely to acquire resistance-conferring mutations in gyrA/B and parC/E. We hypothesize that FQ-resistance imposes a lower fitness cost on exoU compared to exoS strains, thus allowing for better adaptation to the FQ-rich clinical environment. We created isogenic mutants containing a common FQ-resistance conferring point mutation in parC from three exoU to three exoS clinical isolates and tested fitness in vitro using head-to-head competition assays. The mutation differentially affected fitness in the exoU and exoS strains tested. While the addition of the parC mutation dramatically increased fitness in one of the exoU strains leaving the other two unaffected, all three exoS strains displayed a general decrease in fitness. In addition, we found that exoU strains may be able to compensate for the fitness costs associated with the mutation through better regulation of supercoiling compared to the exoS strains. These results may provide a biological explanation for the observed predominance of the virulent exoU genotype in FQ-resistant clinical subpopulations and represent the first investigation into potential differences in fitness costs of FQ-resistance that are linked to the virulence genotype of P. aeruginosa. Understanding the fitness costs of antibiotic resistance and possibilities of compensation for these costs is essential for the rational development of strategies to combat the problem of antibiotic resistance.

  17. Accelerated split-course (Type B) thoracic radiation therapy plus vinorelbine/carboplatin combination chemotherapy in Stage III inoperable non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iaffaioli, R.V.; Tortoriello, A.; Facchini, G.; Maccauro, M.; Dimitri, P. [Cagliari Univ. (Italy). Ist. Medicina Interna; Caponigro, F. [Istituto Medico Legale, Milan (Italy); Ravo, V.; Muto, P. [Naples Univ. (Italy). Ist. Scienze Radiologiche; Crovella, F. [Ospedale Oliveto, Citra (Italy). Div. Chirurgia Generale

    1996-10-01

    43 patients with stage III NSCLC (non-small cell lung cancer) entered a phase II study aimed at evaluating the toxicity and the activity of a combined modality programme including an accelerated split-course schedule (type B) of thoracic radiation therapy and a combination chemotherapy with vinorelbine and carboplatin. An objective response was achieved in 18/42 evaluable patients (5 complete and 13 partial responses), for an overall response rate of 43% (95% confidence interval, 28-58%). Four complete responses had a duration which exceeded 16 months. Treatment was well tolerated; grade III myelotoxicity occurred in only 14% of patients and treatment was delayed in only 2 cases because of grade 3 oesophagitis. Both tolerability and efficacy data suggest that this regimen holds promise for the treatment of patients with stage III NSCLC. (author).

  18. Effect of obesity and exercise on the expression of the novel myokines, Myonectin and Fibronectin type III domain containing 5

    Directory of Open Access Journals (Sweden)

    Jonathan M. Peterson

    2014-09-01

    Full Text Available Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, Myonectin and Fibronectin type III domain containing 5 (FNDC5, the precursor for Irisin. Methods. We performed immunoblot analysis and quantitative real-time PCR analysis of Myonectin and FNDC5 in the diaphragm muscles of obese Zucker rat (OZR and lean Zucker rat (LZR with 9 weeks of aerobic training on a motorized treadmill. Results. We show that myonectin gene expression is increased in the OZR model of obesity and decreases with exercise in both lean and obese Zucker rats. Conversely, myonectin protein concentration was elevated with exercise. Similarly, FNDC5 mRNA levels are significantly higher in the OZR, however exercise training had no effect on the expression level of FNDC5 in either the LZR or OZR. We did not observe any difference in muscle protein content of Irisin with obesity or exercise. Conclusion. Our data shows that exercise training does not increase either FNDC5 or myonectin gene expression, indicating that increased transcriptional regulation of these myokines is not induced by exercise. However, our data also indicates a yet to be explored disconnect between myonectin gene expression and protein content. Further, this report highlights the importance of verifying reference genes when completing gene expression analysis. We found that many commonly used reference genes varied significantly by

  19. Compound Specific Hydrogen Isotope Composition of Type II and III Kerogen Extracted by Pyrolysis-GC-MS-IRMS

    Science.gov (United States)

    Socki, Richard A.; Pernia, Denet; Evans, Michael; Fu, Qi; Bissada, Kadry K.; Curiale, Joseph A.; Niles, Paul B.

    2013-01-01

    The use of Hydrogen (H) isotopes in understanding oil and gas resource plays is in its infancy. Described here is a technique for H isotope analysis of organic compounds pyrolyzed from oil and gas shale-derived kerogen. Application of this technique will progress our understanding. This work complements that of Pernia et al. (2013, this meeting) by providing a novel method for the H isotope analysis of specific compounds in the characterization of kerogen extracted by analytically diverse techniques. Hydrogen isotope analyses were carried out entirely "on-line" utilizing a CDS 5000 Pyroprobe connected to a Thermo Trace GC Ultra interfaced with a Thermo MAT 253 IRMS. Also, a split of GC-separated products was sent to a DSQ II quadrupole MS to make semi-quantitative compositional measurements of the extracted compounds. Kerogen samples from five different basins (type II and III) were dehydrated (heated to 80 C overnight in vacuum) and analyzed for their H isotope compositions by Pyrolysis-GC-MS-TC-IRMS. This technique takes pyrolysis products separated via GC and reacts them in a high temperature conversion furnace (1450 C) which quantitatively forms H2, following a modified method of Burgoyne and Hayes, (1998, Anal. Chem., 70, 5136-5141). Samples ranging from approximately 0.5 to 1.0mg in size, were pyrolyzed at 800 C for 30s. Compounds were separated on a Poraplot Q GC column. Hydrogen isotope data from all kerogen samples typically show enrichment in D from low to high molecular weight compounds. Water (H2O) average deltaD = -215.2 (V-SMOW), ranging from -271.8 for the Marcellus Shale to -51.9 for the Polish Shale. Higher molecular weight compounds like toluene (C7H8) have an average deltaD of -89.7 0/00, ranging from -156.0 for the Barnett Shale to -50.0 for the Monterey Shale. We interpret these data as representative of potential H isotope exchange between hydrocarbons and sediment pore water during formation within each basin. Since hydrocarbon H isotopes

  20. Quantification of the physiochemical constraints on the export of spider silk proteins by Salmonella type III secretion

    Directory of Open Access Journals (Sweden)

    Voigt Christopher A

    2010-10-01

    Full Text Available Abstract Background The type III secretion system (T3SS is a molecular machine in gram negative bacteria that exports proteins through both membranes to the extracellular environment. It has been previously demonstrated that the T3SS encoded in Salmonella Pathogenicity Island 1 (SPI-1 can be harnessed to export recombinant proteins. Here, we demonstrate the secretion of a variety of unfolded spider silk proteins and use these data to quantify the constraints of this system with respect to the export of recombinant protein. Results To test how the timing and level of protein expression affects secretion, we designed a hybrid promoter that combines an IPTG-inducible system with a natural genetic circuit that controls effector expression in Salmonella (psicA. LacO operators are placed in various locations in the psicA promoter and the optimal induction occurs when a single operator is placed at the +5nt (234-fold and a lower basal level of expression is achieved when a second operator is placed at -63nt to take advantage of DNA looping. Using this tool, we find that the secretion efficiency (protein secreted divided by total expressed is constant as a function of total expressed. We also demonstrate that the secretion flux peaks at 8 hours. We then use whole gene DNA synthesis to construct codon optimized spider silk genes for full-length (3129 amino acids Latrodectus hesperus dragline silk, Bombyx mori cocoon silk, and Nephila clavipes flagelliform silk and PCR is used to create eight truncations of these genes. These proteins are all unfolded polypeptides and they encompass a variety of length, charge, and amino acid compositions. We find those proteins fewer than 550 amino acids reliably secrete and the probability declines significantly after ~700 amino acids. There also is a charge optimum at -2.4, and secretion efficiency declines for very positively or negatively charged proteins. There is no significant correlation with hydrophobicity

  1. LcrV delivered via type III secretion system of live attenuated Yersinia pseudotuberculosis enhances immunogenicity against pneumonic plague.

    Science.gov (United States)

    Sun, Wei; Sanapala, Shilpa; Henderson, Jeremy C; Sam, Shandiin; Olinzock, Joseph; Trent, M Stephen; Curtiss, Roy

    2014-10-01

    Here, we constructed a Yersinia pseudotuberculosis mutant strain with arabinose-dependent regulated and delayed shutoff of crp expression (araC P(BAD) crp) and replacement of the msbB gene with the Escherichia coli msbB gene to attenuate it. Then, we inserted the asd mutation into this construction to form χ10057 [Δasd-206 ΔmsbB868::P(msbB) msbB(EC) ΔP(crp21)::TT araC P(BAD) crp] for use with a balanced-lethal Asd-positive (Asd(+)) plasmid to facilitate antigen synthesis. A hybrid protein composed of YopE (amino acids [aa]1 to 138) fused with full-length LcrV (YopE(Nt138)-LcrV) was synthesized in χ10057 harboring an Asd(+) plasmid (pYA5199, yopE(Nt138)-lcrV) and could be secreted through a type III secretion system (T3SS) in vitro and in vivo. Animal studies indicated that mice orally immunized with χ10057(pYA5199) developed titers of IgG response to whole-cell lysates of Y. pestis (YpL) and subunit LcrV similar to those seen with χ10057(pYA3332) (χ10057 plus an empty plasmid). However, only immunization of mice with χ10057(pYA5199) resulted in a significant secretory IgA response to LcrV. χ10057(pYA5199) induced a higher level of protection (80% survival) against intranasal (i.n.) challenge with ~240 median lethal doses (LD50) (2.4 × 10(4) CFU) of Y. pestis KIM6+(pCD1Ap) than χ10057(pYA3332) (40% survival). Splenocytes from mice vaccinated with χ10057(pYA5199) produced significant levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-17 (IL-17) after restimulation with LcrV and YpL antigens. Our results suggest that it is possible to use an attenuated Y. pseudotuberculosis strain delivering the LcrV antigen via the T3SS as a potential vaccine candidate against pneumonic plague.

  2. The chicken type III GnRH receptor homologue is predominantly expressed in the pituitary, and exhibits similar ligand selectivity to the type I receptor.

    Science.gov (United States)

    Joseph, Nerine T; Morgan, Kevin; Sellar, Robin; McBride, Derek; Millar, Robert P; Dunn, Ian C

    2009-07-01

    Two GnRH isoforms (cGnRH-I and GnRH-II) and two GnRH receptor subtypes (cGnRH-R-I and cGnRH-R-III) occur in chickens. Differential roles for these molecules in regulating gonadotrophin secretion or other functions are unclear. To investigate this we cloned cGnRH-R-III from a broiler chicken and compared its structure, expression and pharmacological properties with cGnRH-R-I. The broiler cGnRH-R-III cDNA was 100% identical to the sequence reported in the red jungle fowl and white leghorn breed. Pituitary cGnRH-R-III mRNA was approximately 1400-fold more abundant than cGnRH-R-I mRNA. Northern analysis indicated a single cGnRH-R-III transcript. A pronounced sex and age difference existed, with higher pituitary transcript levels in sexually mature females versus juvenile females. In contrast, higher expression levels occurred in juvenile males versus sexually mature males. Functional studies in COS-7 cells indicated that cGnRH-R-III has a higher binding affinity for GnRH-II than cGnRH-I (K(d): 0.57 vs 19.8 nM) with more potent stimulation of inositol phosphate production (ED(50): 0.8 vs 4.38 nM). Similar results were found for cGnRH-R-I, (K(d): 0.51 vs 10.8 nM) and (ED(50): 0.7 vs 2.8 nM). The initial rate of internalisation was faster for cGnRH-R-III than cGnRH-R-I (26 vs 15.8%/min). Effects of GnRH antagonists were compared at the two receptors. Antagonist #27 distinguished between cGnRH-R-I and cGnRH-R-III (IC(50): 2.3 vs 351 nM). These results suggest that cGnRH-R-III is probably the major mediator of pituitary gonadotroph function, that antagonist #27 may allow delineation of receptor subtype function in vitro and in vivo and that tissue-specific recruitment of cGnRH-R isoforms has occurred during evolution. PMID:19380456

  3. Synthesis of Unnatural 2-Substituted Quinolones and 1,3-Diketones by a Member of Type III Polyketide Synthases from Huperzia serrata.

    Science.gov (United States)

    Wang, Juan; Wang, Xiao-Hui; Liu, Xiao; Li, Jun; Shi, Xiao-Ping; Song, Yue-Lin; Zeng, Ke-Wu; Zhang, Le; Tu, Peng-Fei; Shi, She-Po

    2016-08-01

    A curcuminoids, benzalacetone-, and quinolone-producing type III polyketide synthase (HsPKS3) from Huperzia serrata uniquely catalyzes the formation of unnatural 2-substituted quinolones and 1,3-diketones via head-to-head condensation of two completely different substrates. The broad range of substrate tolerance of HsPKS3 facilitates accessing structurally diverse 2-substituted quinolones and 1,3-diketones. PMID:27399835

  4. Expression of mRNAs coding for the alpha 1 chain of type XIII collagen in human fetal tissues: comparison with expression of mRNAs for collagen types I, II, and III

    OpenAIRE

    1989-01-01

    This paper describes the topographic distribution of the multiple mRNAs coding for a novel human short-chain collagen, the alpha 1 chain of type XIII collagen. To identify the tissues and cells expressing these mRNAs, human fetal tissues of 15-19 gestational wk were studied by Northern and in situ hybridizations. The distribution pattern of the type XIII collagen mRNAs was compared with that of fibrillar collagen types I, II, and III using specific human cDNA probes for each collagen type. No...

  5. Multiple activities of the plant pathogen type III effector proteins WtsE and AvrE require WxxxE motifs.

    Science.gov (United States)

    Ham, Jong Hyun; Majerczak, Doris R; Nomura, Kinya; Mecey, Christy; Uribe, Francisco; He, Sheng-Yang; Mackey, David; Coplin, David L

    2009-06-01

    The broadly conserved AvrE-family of type III effectors from gram-negative plant-pathogenic bacteria includes important virulence factors, yet little is known about the mechanisms by which these effectors function inside plant cells to promote disease. We have identified two conserved motifs in AvrE-family effectors: a WxxxE motif and a putative C-terminal endoplasmic reticulum membrane retention/retrieval signal (ERMRS). The WxxxE and ERMRS motifs are both required for the virulence activities of WtsE and AvrE, which are major virulence factors of the corn pathogen Pantoea stewartii subsp. stewartii and the tomato or Arabidopsis pathogen Pseudomonas syringae pv. tomato, respectively. The WxxxE and the predicted ERMRS motifs are also required for other biological activities of WtsE, including elicitation of the hypersensitive response in nonhost plants and suppression of defense responses in Arabidopsis. A family of type III effectors from mammalian bacterial pathogens requires WxxxE and subcellular targeting motifs for virulence functions that involve their ability to mimic activated G-proteins. The conservation of related motifs and their necessity for the function of type III effectors from plant pathogens indicates that disturbing host pathways by mimicking activated host G-proteins may be a virulence mechanism employed by plant pathogens as well. PMID:19445595

  6. Search for Type-III Seesaw Heavy Fermions with Multilepton Final States using 2.3/fb of 13 TeV proton-proton Collision Data

    CERN Document Server

    CMS Collaboration

    2016-01-01

    A search for type-III seesaw signal in events with three or more electrons or muons is presented. The data sample corresponds to $2.3\\,\\textrm{fb}^{-1}$ of integrated luminosity in $pp$ collisions at $\\sqrt{s} = 13\\,$TeV collected by the CMS experiment at the LHC. Since the signal populates channels with at least three leptons and diverse kinematic properties, the data is binned in exclusive channels. The primary selection is based on the number of leptons and the invariant mass of opposite-sign dilepton systems which helps discriminate the signal against the Standard Model background. The final optimization for the type-III seesaw signal is based on the sum of leptonic transerve momenta and missing transverse energy. Control samples in data are used to check the robustness of background evaluation techniques and to minimize the reliance on simulation. The observations are consistent with expectations from Standard Model processes. The results are used to exclude heavy fermions of the type-III seesaw model wi...

  7. Substitution of Aspartate for glycine 1018 in the Type III procollagen (COL3AI) gene causes type IV Ehlers-Danlos Syndrome: The mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother

    Energy Technology Data Exchange (ETDEWEB)

    Kontusaari, S.; Tromp, G.; Kuivaniemi, H.; Prockop, D.J. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Stolle, C. (Robert Wood Johnson Medical School, Piscataway, NJ (United States)); Pope, F.M.

    1992-09-01

    A proband with arterial ruptures and skin changes characteristic of the type IV variant of Ehlers-Danlos syndrome was found to have a single-base mutation in the type III procollagen gene, which converted the codon for glycine at amino position 1018 to a codon for aspartate. (Amino acid positions are numbered by the standard convention in which the first glycine of the triple-helical domain of an [alpha] chain is number 1. The numbers of positions in the [alpha]1(III) chains can be converted to positions in the human pro[alpha](III) chain by adding 167.). Nucleotide sequencing of overlapping PCR products in which the two alleles were distinguished demonstrated that the mutation of glycine 1018 was the only mutation that changed the primary structure of type III procollagen. The glycine substitution markedly decreased the amount of type III procollagen secreted into the medium by cultured skin fibroblasts from the proband. It is surprising that the same mutation was found in about 94% of the peripheral blood leukocytes from the proband's asymptomatic 72-year-old mother. Other tissues from the mother contained the mutated allele; it was present in 0%-100% of different samples of hair cells and in about 40% of cells from the oral epithelium. Therefore, the mother was a mosaic for the mutation. Since the mutated allele was present in cells derived from all three germ layers, the results indicated that the mutation arose by the late blastocyst stage of development. The results also indicate that assays of blood leukocytes do not always reveal mosaicism or predict phenotypic involvement of tissues, such as blood vessels, that are derived from the same embryonic cells as are leukocytes. 66 refs., 6 figs., 1 tab.

  8. The metastability of human UDP-galactose 4'-epimerase (GALE) is increased by variants associated with type III galactosemia but decreased by substrate and cofactor binding

    OpenAIRE

    Angel L Pey; Padín-Gonzalez, Esperanza; Mesa-Torres, Noel; Timson, David J.

    2014-01-01

    Type III galactosemia is an inherited disease caused by mutations which affect the activity of UDP-galactose 4'-epimerase (GALE). We evaluated the impact of four disease-associated variants (p.N34S, p.G90E, p.V94M and p.K161N) on the conformational stability and dynamics of GALE. Thermal denaturation studies showed that wild-type GALE denatures at temperatures close to physiological, and disease-associated mutations often reduce GALE's thermal stability. This denaturation is under kinetic con...

  9. Effect of the Salmonella Pathogenicity Island 2 Type III Secretion System on Salmonella Survival in Activated Chicken Macrophage-Like HD11 Cells

    OpenAIRE

    Wisner, Amanda L. S.; Potter, Andrew A.; Köster, Wolfgang

    2011-01-01

    In order to better identify the role of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (T3SS) in chickens, we used the well-known gentamicin protection assay with activated HD11 cells. HD11 cells are a macrophage-like chicken cell line that can be stimulated with phorbol 12-myristate 13-acetate (PMA) to exhibit more macrophage-like morphology and greater production of reactive oxygen species (ROS). Activated HD11 cells were infected with a wild-type Salmonella enteric...

  10. Evidence for the co-circulation of dengue virus type 3 genotypes III and V in the Northern region of Brazil during the 2002-2004 epidemics

    Directory of Open Access Journals (Sweden)

    Meri Bordignon Nogueira

    2008-08-01

    Full Text Available The reintroduction of dengue virus type 3 (DENV-3 in Brazil in 2000 and its subsequent spread throughout the country was associated with genotype III viruses, the only DENV-3 genotype isolated in Brazil prior to 2002. We report here the co-circulation of two different DENV-3 genotypes in patients living in the Northern region of Brazil during the 2002-2004 epidemics. Complete genomic sequences of viral RNA were determined from these epidemics, and viruses belonging to genotypes V (Southeast Asia/South Pacific and III were identified. This recent co-circulation of different DENV-3 genotypes in South America may have implications for pathological and epidemiological dynamics.

  11. Hybrid MPI-OpenMP Paradigm on SMP Clusters: MPEG-2 Encoder and N-Body Simulation

    OpenAIRE

    Duy, Truong Vinh Truong; Yamazaki, Katsuhiro; Ikegami, Kosai; Oyanagi, Shigeru

    2012-01-01

    Clusters of SMP nodes provide support for a wide diversity of parallel programming paradigms. Combining both shared memory and message passing parallelizations within the same application, the hybrid MPI-OpenMP paradigm is an emerging trend for parallel programming to fully exploit distributed shared-memory architecture. In this paper, we improve the performance of MPEG-2 encoder and n-body simulation by employing the hybrid MPI-OpenMP programming paradigm on SMP clusters. The hierarchical im...

  12. New lethal disease involving type I and III collagen defect resembling geroderma osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV.

    Science.gov (United States)

    Jukkola, A; Kauppila, S; Risteli, L; Vuopala, K; Risteli, J; Leisti, J; Pajunen, L

    1998-06-01

    We describe the clinical findings and biochemical features of a male child suffering from a so far undescribed lethal connective tissue disorder characterised by extreme hypermobility of the joints, lax skin, cataracts, severe growth retardation, and insufficient production of type I and type III procollagens. His features are compared with Ehlers-Danlos type IV, De Barsy syndrome, and geroderma osteodysplastica, as these disorders show some symptoms and signs shared with our patient. The child died because of failure of the connective tissue structures joining the skull and the spine, leading to progressive spinal stenosis. The aortic valve was translucent and insufficient. The clinical symptoms and signs, together with histological findings, suggested a collagen defect. Studies on both skin fibroblast cultures and the patient's serum showed reduced synthesis of collagen types I and III at the protein and RNA levels. The sizes of the mRNAs and newly synthesised proteins were normal, excluding gross structural abnormalities. These findings are not in accordance with any other collagen defect characterised so far.

  13. Enterohemorrhagic E. coli requires N-WASP for efficient type III translocation but not for EspFU-mediated actin pedestal formation.

    Directory of Open Access Journals (Sweden)

    Didier Vingadassalom

    Full Text Available Upon infection of mammalian cells, enterohemorrhagic E. coli (EHEC O157:H7 utilizes a type III secretion system to translocate the effectors Tir and EspF(U (aka TccP that trigger the formation of F-actin-rich 'pedestals' beneath bound bacteria. EspF(U is localized to the plasma membrane by Tir and binds the nucleation-promoting factor N-WASP, which in turn activates the Arp2/3 actin assembly complex. Although N-WASP has been shown to be required for EHEC pedestal formation, the precise steps in the process that it influences have not been determined. We found that N-WASP and actin assembly promote EHEC-mediated translocation of Tir and EspF(U into mammalian host cells. When we utilized the related pathogen enteropathogenic E. coli to enhance type III translocation of EHEC Tir and EspF(U, we found surprisingly that actin pedestals were generated on N-WASP-deficient cells. Similar to pedestal formation on wild type cells, Tir and EspF(U were the only bacterial effectors required for pedestal formation, and the EspF(U sequences required to interact with N-WASP were found to also be essential to stimulate this alternate actin assembly pathway. In the absence of N-WASP, the Arp2/3 complex was both recruited to sites of bacterial attachment and required for actin assembly. Our results indicate that actin assembly facilitates type III translocation, and reveal that EspF(U, presumably by recruiting an alternate host factor that can signal to the Arp2/3 complex, exhibits remarkable versatility in its strategies for stimulating actin polymerization.

  14. Type I and III IFNs Produced by Plasmacytoid Dendritic Cells in Response to a Member of the Flaviviridae Suppress Cellular Immune Responses.

    Science.gov (United States)

    Reid, Elizabeth; Juleff, Nicholas; Windsor, Miriam; Gubbins, Simon; Roberts, Lisa; Morgan, Sophie; Meyers, Gregor; Perez-Martin, Eva; Tchilian, Elma; Charleston, Bryan; Seago, Julian

    2016-05-15

    The pestivirus noncytopathic bovine viral diarrhea virus (BVDV) can suppress IFN production in the majority of cell types in vitro. However, IFN is detectable in serum during acute infection in vivo for ∼5-7 d, which correlates with a period of leucopoenia and immunosuppression. In this study, we demonstrate that a highly enriched population of bovine plasmacytoid dendritic cells (DCs) produced IFN in response to BVDV in vitro. We further show that the majority of the IFN produced in response to infection both in vitro and in vivo is type III IFN and acid labile. Further, we show IL-28B (IFN-λ3) mRNA is induced in this cell population in vitro. Supernatant from plasmacytoid DCs harvested postinfection with BVDV or recombinant bovine IFN-α or human IL-28B significantly reduced CD4(+) T cell proliferation induced by tubercle bacillus Ag 85-stimulated monocyte-derived DCs. Furthermore, these IFNs induced IFN-stimulated gene expression predominantly in monocyte-derived DCs. IFN-treated immature DCs derived from murine bone marrow also had a reduced capacity to stimulate T cell proliferative responses to tubercle bacillus Ag 85. Immature DCs derived from either source had a reduced capacity for Ag uptake following IFN treatment that is dose dependent. Immunosuppression is a feature of a number of pestivirus infections; our studies suggest type III IFN production plays a key role in the pathogenesis of this family of viruses. Overall, in a natural host, we have demonstrated a link between the induction of type I and III IFN after acute viral infection and transient immunosuppression. PMID:27053760

  15. Ehlers-Danlos Syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen

    Energy Technology Data Exchange (ETDEWEB)

    Superti-Furga, A.; Gugler, E.; Gitzelmann, R.; Steinmann, B.

    1988-05-05

    The authors have studied a patient with severe, dominantly inherited Ehlers-Danlos syndrome type IV. The results indicate that this patient carries a deletion of 3.3 kilobase pairs in the triple helical coding domain of one of the two alleles for the pro-..cap alpha..-chains of type III collagen (COL3A1). His cultured skin fibroblasts contain equal amounts of normal length mRNA and of mRNA shortened by approximately 600 bases, and synthesize both normal and shortened pro-..cap alpha..1(III)-chains. In procollagen molecules containing one or more shortened chains, a triple helix is formed with a length of only about 780 amino acids. The mutant procollagen molecules have decreased thermal stability, are less efficiently secreted, and are not processed as their normal counterpart. The deletion in this family is the first mutation to be described in COL3A1.

  16. Charged lepton flavour violcxmation and neutrinoless double beta decay in left-right symmetric models with type I+II seesaw

    Science.gov (United States)

    Borah, Debasish; Dasgupta, Arnab

    2016-07-01

    We study the new physics contributions to neutrinoless double beta decay (0 νββ) half-life and lepton flavour violation (LFV) amplitude within the framework of the minimal left-right symmetric model (MLRSM). Considering all possible new physics contributions to 0 νββ and charged lepton flavour violation μ → eγ , μ → 3 e in MLRSM, we constrain the parameter space of the model from the requirement of satisfying existing experimental bounds. Assuming the breaking scale of the left-right symmetry to be O (1) TeV accessible at ongoing and near future collider experiments, we consider the most general type I+II seesaw mechanism for the origin of tiny neutrino masses. Choosing the relative contribution of the type II seesaw term allows us to calculate the right handed neutrino mass matrix as well as Dirac neutrino mass matrix as a function of the model parameters, required for the calculation of 0νββ and LFV amplitudes. We show that such a general type I+II seesaw structure results in more allowed parameter space compared to individual type I or type II seesaw cases considered in earlier works. In particular, we show that the doubly charged scalar masses M Δ are allowed to be smaller than the heaviest right handed neutrino mass M N from the present experimental bounds in these scenarios which is in contrast to earlier results with individual type I or type II seesaw showing M Δ > M N .

  17. Measurement of matrix metalloproteinase 9-mediated Collagen type III degradation fragment as a marker of skin fibrosis

    Directory of Open Access Journals (Sweden)

    Larsen Lise

    2011-03-01

    Full Text Available Abstract Background The current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP, a fragment of collagen III released during matrix metalloproteinase-9 (MMP9 degradation of the protein, we have previously described as a novel biomarker for liver fibrosis. The aim was to investigate CO3-610 levels in another well characterised model of fibrosis, to better describe the biomarker in relation to additional fibrotic pathologies. Methods Skin fibrosis was induced by daily injections of Bleomycin to a total of 52 female C3 H mice, while control mice (n = 28 were treated with phosphate buffered saline (PBS, for 2, 4, 6 or 8 weeks. Skin fibrosis was evaluated using Visiopharm software on Sirius-red stained skin sections. Urine ELISA assays and creatinine corrections were performed to measure CO3-610 levels. Results CO3-610 levels were significantly higher in Bleomycin-treated vs. PBS-treated mice at each time point of termination. The mean increases were: 59.2%, P Conclusion Increased levels in mouse urine of the MMP-9 mediated collagen III degradation fragment CO3-610 were correlated with skin fibrosis progression, suggesting that CO3-610 may be a potential positive biomarker to study the pathogenesis of skin fibrosis in mice.

  18. Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice.

    Directory of Open Access Journals (Sweden)

    Guo Chen

    2011-09-01

    Full Text Available BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice. METHODOLOGY/PRINCIPAL FINDINGS: Promoters (nirB or pagC were used to express the antigen (Sj23LHDGST and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104-Sj23LHD-GST efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69. CONCLUSION/SIGNIFICANCE: Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.

  19. Tratamiento de una lesión endoperiodontal tipo III (combinada o verdadera: reporte de un caso Treatment of type III periodontal-endodontic lesion (combined or true: a case report

    Directory of Open Access Journals (Sweden)

    M Alcota

    2011-04-01

    Full Text Available Se presenta un caso clínico de una lesión endoperiodontal tipo III (combinada o verdadera en un paciente de sexo femenino de 41 años de edad sin antecedentes sistémicos. La paciente fue derivada del Curso de Especialización en Periodoncia de la Escuela de Graduados de la Universidad de Chile debido a una lesión periapical en la pieza 3.6. El pronóstico en este tipo de lesiones es dudoso, ya que es necesario que se efectúe el tratamiento endodóntico así como el periodontal, y el resultado recae más en el tratamiento periodontal. La pieza fue tratada endodónticamente dejando medicamento intraconducto a base de Clorhexidina al 2% en gel por 7 días. Una vez obturado el diente se citó a la paciente 3 meses después para un control radiográfico. Actualmente el diente está totalmente asintomático, sin movilidad y con señales de reparación.We report a case of a type III periodontal-endodontic lesion (combined or true in a 41-year-old female patient without systemic history. The patient was transferred from the Specialization Course in Periodontology at the Graduate School of the University of Chile due to a periapical lesion in the tooth 3.6. The prognosis for this type of lesion is uncertain, since it is necessary to perform endodontic and periodontal treatment, and the result depends more on the periodontal treatment. The piece was treated endodontically leaving intracanal medication based on 2% Chlorhexidine gel for 7 days. Once the tooth obturated, we gave the patient an appointment 3 months later for a control radiography. Currently, the tooth is completely asymptomatic, without mobility and with signs of repair.

  20. Targeted next-generation sequencing identifies novel compound heterozygous mutations of DYNC2H1 in a fetus with short rib-polydactyly syndrome, type III.

    Science.gov (United States)

    Mei, Libin; Huang, Yanru; Pan, Qian; Su, Wei; Quan, Yi; Liang, Desheng; Wu, Lingqian

    2015-07-20

    A 26-year-old woman with a past history of fetal skeletal dysplasia was referred to our institution at 24weeks of gestation following a routine sonographic diagnosis of short limbs in the fetus. A fetal ultrasound showed short limbs, a narrow thorax, short ribs with marginal spurs, and polydactyly. Conventional cytogenetics analysis of cultured amniocytes demonstrated that the fetal karyotype was normal. Using targeted exome sequencing of 226 known genes implicated in inherited skeletal dysplasia, we identified compound heterozygous mutations in the DYNC2H1 gene in the fetus with short rib-polydactyly syndrome, type III (SRPS III), c.1151 C>T(p.Ala384Val) and c.4351 C>T (p.Gln1451*), which were inherited from paternally and maternally, respectively. These variants were further confirmed using Sanger sequencing and have not been previously reported. To our knowledge, this is the first report of DYNC2H1 mutations causing SRPS III, in the Chinese population. Our findings expand the number of reported cases of this rare disease, and indicate that targeted next-generation sequencing (NGS) is an accurate, rapid, and cost-effective method in the genetic diagnosis of fetal skeletal dysplasia.

  1. A conserved domain in type III secretion links the cytoplasmic domain of InvA to elements of the basal body

    Energy Technology Data Exchange (ETDEWEB)

    Lilic, Mirjana; Quezada, Cindy M.; Stebbins, C. Erec, E-mail: stebbins@rockefeller.edu [Laboratory of Structural Microbiology, The Rockefeller University, New York, NY 10065 (United States)

    2010-06-01

    The cytoplasmic domain of Salmonella InvA shares homology to a recurring scaffold in the membrane-spanning components of the type II and type III secretion systems. Protein type III secretion systems (T3SSs) are organic nanosyringes that achieve an energy-dependent translocation of bacterial proteins through the two membranes of Gram-negative organisms. Examples include the pathogenic systems of animals, plants and symbiotic bacteria that inject factors into eukaryotic cells, and the flagellar export system that secretes flagellin. T3SSs possess a core of several membrane-associated proteins that are conserved across all known bacterial species that use this system. The Salmonella protein InvA is one of the most highly conserved proteins of this core of critical T3SS components. The crystal structure of a C-terminal domain of InvA reveals an unexpected homology to domains that have been repeatedly found as building blocks of other elements of the T3SS apparatus. This suggests the surprising hypothesis that evolution has produced a significant component of the apparatus structure through a series of gene-duplication and gene-rearrangement events.

  2. A Geobacter sulfurreducens Strain Expressing Pseudomonas aeruginosa Type IV Pili Localizes OmcS on Pili but Is Deficient in Fe(III) Oxide Reduction and Current Production

    Science.gov (United States)

    Liu, Xing; Tremblay, Pier-Luc; Malvankar, Nikhil S.; Nevin, Kelly P.; Vargas, Madeline

    2014-01-01

    The conductive pili of Geobacter species play an important role in electron transfer to Fe(III) oxides, in long-range electron transport through current-producing biofilms, and in direct interspecies electron transfer. Although multiple lines of evidence have indicated that the pili of Geobacter sulfurreducens have a metal-like conductivity, independent of the presence of c-type cytochromes, this claim is still controversial. In order to further investigate this phenomenon, a strain of G. sulfurreducens, designated strain PA, was constructed in which the gene for the native PilA, the structural pilin protein, was replaced with the PilA gene of Pseudomonas aeruginosa PAO1. Strain PA expressed and properly assembled P. aeruginosa PilA subunits into pili and exhibited a profile of outer surface c-type cytochromes similar to that of a control strain expressing the G. sulfurreducens PilA. Surprisingly, the strain PA pili were decorated with the c-type cytochrome OmcS in a manner similar to the control strain. However, the strain PA pili were 14-fold less conductive than the pili of the control strain, and strain PA was severely impaired in Fe(III) oxide reduction and current production. These results demonstrate that the presence of OmcS on pili is not sufficient to confer conductivity to pili and suggest that there are unique structural features of the G. sulfurreducens PilA that are necessary for conductivity. PMID:24296506

  3. Multiple Activities of the Plant Pathogen Type III Effector Proteins WtsE and AvrE1 require WxxxE Motifs

    OpenAIRE

    Ham, Jong Hyun; Majerczak, Doris R.; Nomura, Kinya; Mecey, Christy; Uribe, Francisco de, (S.I.) (1613-1667); He, Sheng-Yang; Mackey, David; Coplin, David L.

    2009-01-01

    The broadly conserved AvrE-family of type III effectors from Gram-negative plant pathogenic bacteria includes important virulence factors, yet little is known about the mechanisms by which these effectors function inside plant cells to promote disease. We have identified two conserved motifs in AvrE-family effectors: a WxxxE motif and a putative C-terminal endoplasmic reticulum membrane retention/retrieval signal (ERMRS). The WxxxE and ERMRS motifs are both required for the virulence activiti...

  4. Fibronectin type III (FN3) modules of the neuronal cell adhesion molecule L1 interact directly with the fibroblast growth factor (FGF) receptor

    DEFF Research Database (Denmark)

    Kulahin, Nikolaj; Li, Shizhong; Hinsby, Anders Mørkeberg;

    2008-01-01

    The neuronal cell adhesion molecule (CAM) L1 promotes axonal outgrowth, presumably through an interaction with the fibroblast growth factor receptor (FGFR). The present study demonstrates a direct interaction between L1 fibronectin type III (FN3) modules I-V and FGFR1 immunoglobulin (Ig) modules II...... receptor phosphorylation, and this resulted in the induction of differentiation of primary neurons, reflected by neurite outgrowth. Furthermore, ATP modulated L1-induced neuronal differentiation and FGFR1 phosphorylation through regulation of the L1-FGFR1 interaction....

  5. Precise investigation of the axial ligand substitution mechanism on a hydrogenphosphato-bridged lantern-type platinum(III) binuclear complex in acidic aqueous solution.

    Science.gov (United States)

    Iwatsuki, Satoshi; Mizushima, Chiho; Morimoto, Naoyuki; Muranaka, Shinji; Ishihara, Koji; Matsumoto, Kazuko

    2005-10-31

    Detailed equilibrium and kinetic studies on axial water ligand substitution reactions of the "lantern-type" platinum(III) binuclear complex, [Pt(2)(mu-HPO(4))(4)(H(2)O)(2)](2)(-), with halide and pseudo-halide ions (X(-) = Cl(-), Br(-), and SCN(-)) were carried out in acidic aqueous solution at 25 degrees C with I = 1.0 M. The diaqua Pt(III) dimer complex is in acid dissociation equilibrium in aqueous solution with -log K(h1) = 2.69 +/- 0.04. The consecutive formation constants of the aquahalo complex () and the dihalo complex () were determined spectrophotometrically to be log = 2.36 +/- 0.01 and log = 1.47 +/- 0.01 for the reaction with Cl(-) and log = 2.90 +/- 0.04 and log = 2.28 +/- 0.01 for the reaction with Br(-), respectively. In the kinetic measurements carried out under the pseudo-first-order conditions with a large excess concentration of halide ion compared to that of Pt(III) dimer (C(X)()- > C(Pt)), all of the reactions proceeded via a one-step first-order reaction, which is a contrast to the consecutive two-step reaction for the amidato-bridged platinum(III) binuclear complexes. The conditional first-order rate constant (k(obs)) depended on C(X)()- as well as the acidity of the solution. From kinetic analyses, the rate-limiting step was determined to be the first substitution process that forms the monohalo species, which is in rapid equilibrium with the dihalo complex. The reaction with 4-penten-1-ol was also kinetically investigated to examine the reactivity of the lantern complex with olefin compounds.

  6. Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen--A novel biomarker of atherosclerotic plaque remodeling

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Vassiliadis, Efstathios; Larsen, Lise;

    2011-01-01

    Degradation of collagen in the arterial wall by matrix metalloproteinases is the hallmark of atherosclerosis. We have developed an ELISA for the quantification of type III collagen degradation mediated by MMP-9 in urine....

  7. High-Pressure Raman and Calorimetry Studies of Vanadium(III) Alkyl Hydrides for Kubas-Type Hydrogen Storage.

    Science.gov (United States)

    Morris, Leah; Trudeau, Michel L; Reed, Daniel; Book, David; Antonelli, David M

    2016-03-16

    Reversible hydrogen storage under ambient conditions has been identified as a major bottleneck in enabling a future hydrogen economy. Herein, we report an amorphous vanadium(III) alkyl hydride gel that binds hydrogen through the Kubas interaction. The material possesses a gravimetric adsorption capacity of 5.42 wt % H2 at 120 bar and 298 K reversibly at saturation with no loss of capacity after ten cycles. This corresponds to a volumetric capacity of 75.4 kgH2  m(-3) . Raman experiments at 100 bar confirm that Kubas binding is involved in the adsorption mechanism. The material possesses an enthalpy of H2 adsorption of +0.52 kJ mol(-1) H2 , as measured directly by calorimetry, and this is practical for use in a vehicles without a complex heat management system. PMID:26762590

  8. High-Pressure Raman and Calorimetry Studies of Vanadium(III) Alkyl Hydrides for Kubas-Type Hydrogen Storage.

    Science.gov (United States)

    Morris, Leah; Trudeau, Michel L; Reed, Daniel; Book, David; Antonelli, David M

    2016-03-16

    Reversible hydrogen storage under ambient conditions has been identified as a major bottleneck in enabling a future hydrogen economy. Herein, we report an amorphous vanadium(III) alkyl hydride gel that binds hydrogen through the Kubas interaction. The material possesses a gravimetric adsorption capacity of 5.42 wt % H2 at 120 bar and 298 K reversibly at saturation with no loss of capacity after ten cycles. This corresponds to a volumetric capacity of 75.4 kgH2  m(-3) . Raman experiments at 100 bar confirm that Kubas binding is involved in the adsorption mechanism. The material possesses an enthalpy of H2 adsorption of +0.52 kJ mol(-1) H2 , as measured directly by calorimetry, and this is practical for use in a vehicles without a complex heat management system.

  9. Protein Binding between PcrG-PcrV and PcrH-PopB/PopD Encoded by the pcrGVH-popBD Operon of the Pseudomonas aeruginosa Type III Secretion System

    OpenAIRE

    Allmond, Leonard R.; Karaca, Timur J.; Nguyen, Vinh N.; Nguyen, Thong; Wiener-Kronish, Jeanine P.; Sawa, Teiji

    2003-01-01

    Of the proteins encoded by the pcrGVH-popBD operon of the Pseudomonas aeruginosa type III secretion system, PcrG bound to PcrV and PcrH bound to PopB/PopD. In addition, Yersinia LcrG bound to PcrV, and Yersinia LcrH bound to PopD. The results imply a highly functional conservation of type III secretion between P. aeruginosa and Yersinia species.

  10. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, MPM; VanLeeuwen, AM; Hollema, H; Quint, WGV; Pieters, WJLM

    1997-01-01

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group compr

  11. Involvement of SPI-2-encoded SpiC in flagellum synthesis in Salmonella enterica serovar Typhimurium

    Directory of Open Access Journals (Sweden)

    Sugita Asami

    2009-08-01

    Full Text Available Abstract Background SpiC encoded within Salmonella pathogenicity island 2 on the Salmonella enterica serovar Typhimurium chromosome is required for survival within macrophages and systemic infection in mice. Additionally, SpiC contributes to Salmonella-induced activation of the signal transduction pathways in macrophages by affecting the expression of FliC, a component of flagella filaments. Here, we show the contribution of SpiC in flagellum synthesis. Results Quantitative RT-PCR shows that the expression levels of the class 3 fliD and motA genes that encode for the flagella cap and motor torque proteins, respectively, were lower for a spiC mutant strain than for the wild-type Salmonella. Further, this mutant had lower expression levels of the class 2 genes including the fliA gene encoding the flagellar-specific alternative sigma factor. We also found differences in flagella assembly between the wild-type strain and the spiC mutant. Many flagella filaments were observed on the bacterial surface of the wild-type strain, whereas the spiC mutant had only few flagella. The absence of spiC led to reduced expression of the FlhD protein, which functions as the master regulator in flagella gene expression, although no significant difference at the transcription level of the flhDC operon was observed between the wild-type strain and the spiC mutant. Conclusion The data show that SpiC is involved in flagella assembly by affecting the post-transcription expression of flhDC.

  12. The Pseudomonas syringae Type III Effector AvrRpt2 Promotes Pathogen Virulence via Stimulating Arabidopsis Auxin/Indole Acetic Acid Protein Turnover1[C][W][OA

    Science.gov (United States)

    Cui, Fuhao; Wu, Shujing; Sun, Wenxian; Coaker, Gitta; Kunkel, Barbara; He, Ping; Shan, Libo

    2013-01-01

    To accomplish successful infection, pathogens deploy complex strategies to interfere with host defense systems and subvert host physiology to favor pathogen survival and multiplication. Modulation of plant auxin physiology and signaling is emerging as a common virulence strategy for phytobacteria to cause diseases. However, the underlying mechanisms remain largely elusive. We have previously shown that the Pseudomonas syringae type III effector AvrRpt2 alters Arabidopsis (Arabidopsis thaliana) auxin physiology. Here, we report that AvrRpt2 promotes auxin response by stimulating the turnover of auxin/indole acetic acid (Aux/IAA) proteins, the key negative regulators in auxin signaling. AvrRpt2 acts additively with auxin to stimulate Aux/IAA turnover, suggesting distinct, yet proteasome-dependent, mechanisms operated by AvrRpt2 and auxin to control Aux/IAA stability. Cysteine protease activity is required for AvrRpt2-stimulated auxin signaling and Aux/IAA degradation. Importantly, transgenic plants expressing the dominant axr2-1 mutation recalcitrant to AvrRpt2-mediated degradation ameliorated the virulence functions of AvrRpt2 but did not alter the avirulent function mediated by the corresponding RPS2 resistance protein. Thus, promoting auxin response via modulating the stability of the key transcription repressors Aux/IAA is a mechanism used by the bacterial type III effector AvrRpt2 to promote pathogenicity. PMID:23632856

  13. Analysis of new type III effectors from Xanthomonas uncovers XopB and XopS as suppressors of plant immunity.

    Science.gov (United States)

    Schulze, Sebastian; Kay, Sabine; Büttner, Daniela; Egler, Monique; Eschen-Lippold, Lennart; Hause, Gerd; Krüger, Antje; Lee, Justin; Müller, Oliver; Scheel, Dierk; Szczesny, Robert; Thieme, Frank; Bonas, Ulla

    2012-09-01

    The pathogenicity of the Gram-negative plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv) is dependent on type III effectors (T3Es) that are injected into plant cells by a type III secretion system and interfere with cellular processes to the benefit of the pathogen. In this study, we analyzed eight T3Es from Xcv strain 85-10, six of which were newly identified effectors. Genetic studies and protoplast expression assays revealed that XopB and XopS contribute to disease symptoms and bacterial growth, and suppress pathogen-associated molecular pattern (PAMP)-triggered plant defense gene expression. In addition, XopB inhibits cell death reactions induced by different T3Es, thus suppressing defense responses related to both PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). XopB localizes to the Golgi apparatus and cytoplasm of the plant cell and interferes with eukaryotic vesicle trafficking. Interestingly, a XopB point mutant derivative was defective in the suppression of ETI-related responses, but still interfered with vesicle trafficking and was only slightly affected with regard to the suppression of defense gene induction. This suggests that XopB-mediated suppression of PTI and ETI is dependent on different mechanisms that can be functionally separated. PMID:22738163

  14. Crystallization and preliminary X-ray analysis of FliJ, a cytoplasmic component of the flagellar type III protein-export apparatus from Salmonella sp

    International Nuclear Information System (INIS)

    FliJ is one of the essential cytoplasmic components of the flagellar type III protein-export apparatus; it has been expressed, produced and crystallized and the crystals have been characterized by X-ray diffraction. The axial component proteins of the bacterial flagellum are synthesized in the cytoplasm and then translocated into the central channel of the flagellum by the flagellar type III protein-export apparatus for self-assembly at the distal growing end of the flagellum. FliJ is an essential cytoplasmic component of the export apparatus. In this study, Salmonella FliJ with an extra three residues (glycine, serine and histidine) attached to the N-terminus as the remainder of a His tag (GSH-FliJ) was purified and crystallized. Crystals were obtained by the sitting-drop vapour-diffusion technique using PEG 300 as a precipitant. GSH-FliJ crystals grew in the hexagonal space group P6122 or P6522. While the native crystals diffracted to 3.3 Å resolution, the diffraction resolution limit of mercury derivatives was extended to 2.1 Å. Anomalous and isomorphous difference Patterson maps of the mercury-derivative crystal showed significant peaks in their Harker sections, indicating the usefulness of the derivative data for structure determination

  15. Cysteine proteinase type III is protective against Leishmania infantum infection in BALB/c mice and highly antigenic in visceral leishmaniasis individuals.

    Science.gov (United States)

    Khoshgoo, Naghmeh; Zahedifard, Farnaz; Azizi, Hiva; Taslimi, Yasaman; Alonso, Maribel Jiménez; Rafati, Sima

    2008-10-29

    Visceral leishmaniasis is the most acute form of leishmaniasis and vaccination is the best approach to control it. One of the major groups of virulence factors in Leishmania belongs to cysteine proteinase family. In this study, for the first time, the protective potential of Leishmania infantum cysteine proteinase type III (CPC) by using a prime-boost strategy is evaluated in BALB/c mice. The experiment was carried out in three groups of mice. Vaccinated group was primed with pcDNA-cpc and boosted with rCPC-DHFR in combination with CpG motif and Montanide 720 as adjuvant. Control groups received pcDNA and rDHFR or PBS. The ratio of IgG2a/IgG1, nitric oxide concentration and IFN-gamma induction in vaccinated group is significantly higher than controls. Furthermore, the parasite load of vaccinated group is significantly lower than controls. In addition, sera reactivity of visceral leishmaniasis individuals was examined and showed considerable reactivities toward rCPC in comparison with cutaneous leishmaniasis. The achieved result is highly encouraging the use of cysteine proteinases types I, II and III as vaccine candidate against visceral leishmaniasis.

  16. The Optical Gravitational Lensing Experiment. The OGLE-III Catalog of Variable Stars. XIV. Classical and Type II Cepheids in the Galactic Bulge

    CERN Document Server

    Soszynski, I; Pietrukowicz, P; Szymanski, M K; Kubiak, M; Pietrzynski, G; Wyrzykowski, L; Ulaczyk, K; Poleski, R; Kozlowski, S

    2011-01-01

    The fourteenth part of the OGLE-III Catalog of Variable Stars (OIII-CVS) contains Cepheid variables detected in the OGLE-II and OGLE-III fields toward the Galactic bulge. The catalog is divided into two main categories: 32 classical Cepheids (21 single-mode fundamental-mode F, four first-overtone 1O, two double-mode F/1O, three double-mode 1O/2O and two triple-mode 1O/2O/3O pulsators) and 335 type II Cepheids (156 BL Her, 128 W Vir and 51 RV Tau stars). Six of the type II Cepheids likely belong to the Sagittarius Dwarf Spheroidal Galaxy. The catalog data include the time-series photometry collected in the course of the OGLE survey, observational parameters of the stars, finding charts, and cross-identifications with the General Catalogue of Variable Stars. We discuss some statistical properties of the sample and compare it with the OGLE catalogs of Cepheids in the Large and Small Magellanic Clouds. Multi-mode classical Cepheids in the Galactic bulge show systematically smaller period ratios than their counter...

  17. A murine model for type III tyrosinemia: lack of immunologically detectable 4-hydroxyphenylpyruvic acid dioxygenase enzyme protein in a novel mouse strain with hypertyrosinemia.

    Science.gov (United States)

    Endo, F; Katoh, H; Yamamoto, S; Matsuda, I

    1991-04-01

    We have characterized a new mutant strain of mouse that has hypertyrosinemia. The blood tyrosine level was persistently high, and increased amounts of 4-hydroxyphenylpyruvic acid and its derivatives were excreted into the urine. Succinylacetone was not detected in urine samples from these mice. All the animals were apparently healthy, and there was no evidence of hepatorenal dysfunction. The hypertyrosinemia was transmitted through an autosomal recessive inheritance. Analyses of hepatic enzymes related to tyrosine metabolism revealed that 4-hydroxyphenylpyruvic acid dioxygenase activity was virtually absent, while fumarylacetoacetase and tyrosine aminotransferases (cytosolic and mitochondrial forms) were normal in these mutant mice. Immunoblot analysis of 4-hydroxyphenylpyruvic acid dioxygenase protein in the liver indicated that the subunit protein of the enzyme was absent. It would appear that hypertyrosinemia in this mutant strain was caused by a genetic defect in 4-hydroxyphenylpyruvic acid dioxygenase. These features are similar to type III tyrosinemia in humans. Analysis of this mutant strain of mouse is expected to provide valuable information on the pathogenesis of human type III tyrosinemia and can also serve as a useful system for studies on tyrosine metabolism.

  18. Crystal structure of the C-terminal domain of the Salmonella type III secretion system export apparatus protein InvA.

    Science.gov (United States)

    Worrall, Liam J; Vuckovic, Marija; Strynadka, Natalie C J

    2010-05-01

    InvA is a prominent inner-membrane component of the Salmonella type III secretion system (T3SS) apparatus, which is responsible for regulating virulence protein export in pathogenic bacteria. InvA is made up of an N-terminal integral membrane domain and a C-terminal cytoplasmic domain that is proposed to form part of a docking platform for the soluble export apparatus proteins notably the T3SS ATPase InvC. Here, we report the novel crystal structure of the C-terminal domain of Salmonella InvA which shows a compact structure composed of four subdomains. The overall structure is unique although the first and second subdomains exhibit structural similarity to the peripheral stalk of the A/V-type ATPase and a ring building motif found in other T3SS proteins respectively.

  19. Salter-Harris type III and IV displaced fracture of the hallux in young gymnasts: A series of four cases at 1-year follow-up.

    Science.gov (United States)

    Perugia, Dario; Fabbri, Mattia; Guidi, Marco; Lepri, Marco; Masi, Vincenzo

    2014-12-01

    The purpose of this study was to describe four exceptional cases of Salter-Harris type III and IV fractures of the proximal phalanx of the hallux in young high-level gymnasts. All gymnasts underwent the same mechanism of injury of hyperadduction, which indicates a role of the abductor hallucis muscle in the genesis and displacement of these fractures. An open reduction and internal fixation was performed to achieve an anatomical reduction and avoid chronic disability. At 1-year follow-up, all patients had an excellent American Orthopaedic Foot and Ankle Society (AOFAS) score (100 points), and there was no shortening or angulation of the first ray and no evidence of degenerative joint disease on X-ray. Moreover, all the gymnasts had returned to pre-injury levels of sporting activity. To our knowledge, there are no previous studies that address these types of injuries and how they are handled in gymnasts. PMID:25457317

  20. Lambda Interferon (IFN-gamma), a Type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Bartholdy, C.;

    2006-01-01

    -alpha/beta)-induced directly by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN-alpha...... potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-alpha reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-lambda in vivo did not affect viral...... load after infection with EMCV or LCMV but did reduce the hepatic viral titer of HSV-2. In a model for a localized HSV-2 infection, we further found that IFN-lambda completely blocked virus replication in the vaginal mucosa and totally prevented development of disease, in contrast to IFN-alpha, which...